Nanotechnology Final

A Review Article On Nanotechnology :Emerging Drug
Delivery System In Healthcare And Medicine
A Dissertation Submitted To The Department In Partial

Fulfillment Of The Requirements For The Degree Of
Bachelors In Pharmacy
SUBMITTED BY:
ID: 201 052 032
A Mission With a Vision
DEPARTMENT OF PHARMACY
PRIMEASIA UNIVERSITY
BANANI,DHAKA
\
22th February 2024
A Review Article On Nanotechnology :Emerging Drug Delivery System In Healthcare And Medicine
Page 1
ACKNOWLEDGEMENT
Firstly, I express my deep gratitude to the Almighty ALLAH who has given me the strength and
opportunity for being able to complete this project work in due time . Without His willingness
and help I could not execute this work.
I wish to profound gratitude to my project supervisor MD Shajalal Reza,Lecturer, Department

of Pharmacy, Primeasia University who has helped me in every step of this project on the topic,
“A Review Article On Nanotechnology :Emerging Drug Delivery System In Healthcare
And Medicine” with his proficient skill supervision by providing me all the information about
this project and obviously for supporting and encourage me mentally.
I would like to express my special thanks of gratitude to our department head Taslima Begum
Chairperson, Department Of Pharmacy ,Primeasia University.As well as, who gave me the
opportunity to do this wonderful project, which helped me in doing a lot of research and I came
to know about so many new thingd,I am really thankful to them.
Finally , I extend my sincere appreciation and gratitude to my beloved parents and all of my
friends for their inspiration and moral support to me during the course of this study.
Although there were some negotiable limitations in my project work, I feel most lucky to
complete my works in time which is a result of the best cooperation of the above persons and
also Department of Pharmacy,Primeasia University.
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List Of Contents
Chapter 1. Introduction ..…………………………………………………………… 6
1.1 What Is Nanotechnolog ……………………………………………………… 7

1.2 History Of Nanotechnology ………………………………………………….. 8
1.3 Nanoparticles …………………………………………………………………. 10
1.4 Properties Of Nanoparticles ………………………………………………….. 11
1.5 Types Of Nanoparticles ………………………………………………………. 12
1.5.1. Micelles …………………………………………………………………... 12
1.5.2 Liposomes ……………………………………………………………….. 12
1.5.3. Microemulsions …………………………………………………………. 13
1.5.4. Dendrimers ……………………………………………………………….. 13
1.5.5. Carbon Nanotubes ……………………………………………………….. 14
1.5.6. Metalic Nanoparticles …………………………………………………… 14
1.5.7. Quantum Dots ……………………………………………………………. 14
1.6. Some Natural Polymers In Nanodrug Delivery ……………………………. 15
1.6.1. Starch ……………………………………………………………………. 15
1.6.2. Chitosan ………………………………………………………………... 15
1.6.3. Gelatin …………………………………………………………………… 16
1.6.4. Hydroxyapatite-Based Nanoparticles ………………………………….. 16
Chapter 2. Literature Review Of Nanotechnology …………………………………… 17
Chapter 3 . Mechanism Of Nanotechnology Across BBB ……………………………. 27
3.1. Mechanism Of Nanotechnology Across BBB ……………………………... 27
3.2. Advantages And Disadvantages Of Nanotechnology ……………………… 28
Chapter 4. Role of Nanocarriers In Major Types Of Cancer ……………………….. 29
4.1. Brain Cancer ………………………………………………………………. 31
4.2. Breast Cancer ……………………………………………………………… 33

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4.3. Lung Cancer ………………………………………………………………. 37
Chapter 5. Drug Deivery Approach ………………………………………………… 38
5.1. Drug Delivery Approach In Skin Diseases ……………………………… 41
5.2. Drug Delivery approach in bone diseases ……………………………….. 42
5.3 . Mechanism of Drug delivery In bone diseases …………………………... 42
5.4. Drug delivery approach in blood diseases ………………………………. 43
Chapter 6. Application Of Nanotechnology In Medical Field ………………………. 44
6.1. application of nanotechnology in pharma science ……………………….. 45
6.1.1. Nanoscience and dryg dose specification …………………………… 46
6.1.2. Nanotechnology and drug delivery ………………………………….. 46
6.1.3. DNA and drug delivery system ………………………………………. 47
6.1.4. Green nanotechnology ………………………………………………. 47
6.1.5. Antiviral and antibacterial application ……………………………... 47
6.2. Application In regenerative medical science ………………………………. 48
6.2.1. Nanotechnology and regenerative medicine ………………………... 49
6.3. Nanotechnology in surgery …………………………………………………. 50
6.3.1. Nanotechnology and Anesthesia induction …………………………. 50
6.3.2. Surgical nanorobotics and nanoelectric medicine …………………... 51
6.3.3. Implantable medical nanogenerators ………………………………... 51
6.4. Application Of Nanotechnology in oncology field ………………………….. 52
6.4.1. Nanotechnology and cancer treatment strategies …………………….. 52
6.4.2. Multifunctional, multimodal based anticancer therapy ……………… 53
6.4.3. Targeted Nanodrug delivery technique for cancer therapy…………… 53
6.4.4. Nanotechnology based dug delivery technique and cancer therapy…… 54
6.5. Application of nanotechnology in dentistry…………………………………. 54

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6.5.1. Nanotechnology, tooth repair, hypersensitivity treatment………….. 55
6.5.2. Tooth repositioning and renaturalization ……………………………. 56
6.6. Nanomedicine and Covid 19 ………………………………………………… 56
6.7. Nanoparticle application in nonparenteral ………………………………… 57
6.7.1. Oral Administration …………………………………………………… 57
6.7.2. Pulmonary Administration……………………………………………… 57
6.7.3. Topical Administratio ………………………………………………….. 58
Chapter 7. Toxicity and safety analysys of nanotechnology …………………………... 59
7.1. Toxicity and safety analysys of nanotechnology ……………………………. 60
7.2 Metal based nanoparticle …………………………………………………….. 61
7.3 Lipid based nanoparticle ……………………………………………………... 61
7.4 Protein based nanoparticle …………………………………………………… 62
Chapter 8. Future prospects regarding nanomedical applications …………………... 63
8.1. Future prospects regarding nanomedical applications ……………………. 65
8.1.1. Emerging nanomaterials ………………………………………………. 65
8.1.2. Theranostics and personalized nanomedicine ...……………………… 66
Chapter 9 . FDA approved and commercial nanomaterials …………………………… 68
9.1. Lipid based nanoparticles ……………………………………………………. 69
9.1.1. Daunoxeme ………………………………………………………………. 70
9.1.2. Onivyde …………………………………………………………………… 70
9.1.3. Cytarabin ………………………………………………………………….. 70
9.1.4. Marqibo ………………………………………………………………….. 70
9.1.5. Amphotericin B …………………………………………………………….. 71
9.2. Polymer based nanoparticles ……………………………………………………… 72
9.2.1. Pegol Certolizumab ………………………………………………………… 72

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9.2.2. Pegaspargase ……………………………………………………………… 73
9.2.3. Pegvisoment ………………………………………………………………. 73
9.2.4. Methox PEG glycol ………………………………………………………. 73
9.2.5. Aprepitant ………………………………………………………………… 75
9.2.6. Sirolimus ………………………………………………………………….. 75
9.2.7. Methylphendat …………………………………………………………….. 75
9.2.8. Dexmethyl Phenidate HCl ………………………………………………… 76
9.2.9. Tizanidine HCl …………………………………………………………. 76
9.3 Regulations of nanomedicine in medical field …………………………………. 77
Chapter 10 Conclusion …………………………………………………………………. 78
Chapter 11 References …………………………………………………………………. 80
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List Of Tables
Table 1. Advantages and disadvantages of nanomedicine …………………………… 29
Table 2. Various nanoparticles involved in brain cancer in recent era ……………… 34
Table 3. Nanoparticle role inTreatment of breast cancer …………………………….. 35
Table 4. Recent discovered nanoparticles role in major cancer ……………………… 37
Table 5. Nanoparticles role in heart diseases ………………………………………….. 39
Table 6. Approved marketed drug loaded lipid based nanoparticle ………………... 69
Table 8. Approved marketed drug loaded polymer based nanoparticle …………… 72
Table 9. Approved marketed drug loaded Crystalline based nanoparticle ………… 74
Table10. Steps needs to regulate industrialization appeairs …………………………... 77
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List Of Figures
Figure 1. Mechanism of nanoparticles across BBB…………………………………….. 27
Figure 2. Mechanism of nanocarriers in breast cancer ……………………………….. 34
Figure 3. Mechanism of drug delivery in skin …………………………………………. 41
Figure 4. Mechanism of drug delivery in bone diseases ……………………………….. 42
Figure 5. Mechanism of drug delivery in blood diseases ………………………………. 43
Figure 6. Applications of nanotechnology in pharmaceutical ………………………… 45
Figure 7. Applications of nanotechnology in surgery …………………………………. 50
Figure 8. Nanotechnology and cancer treatment ……………………………………… 52
Figure 9. Application of nanotechnology in dentistry …………………………………. 55
Figure 10.Toxicity recorded by protein,lipid and metal………………………………… 60
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Abstract
Nanotechnology is the exploitation of the unique properties of materials at the nanoscale.

Nanotechnology has gained popularity in several industries, as it offers better built and smarter
products. The application of nanotechnology in medicine and healthcare is referred to as
nanomedicine, and it has been used to combat some of the most common diseases, including
cardiovascular diseases and cancer. We are using the products develop by nanotechnology on a
daily basic without even knowing it. Nanotechnology is science, engineering and technology
conducted at nanoscale. It deals with the understanding and control of matter at the nanoscale,
dimensions between approximately 1 and 100 nanometers. Nanomedicine is the term for the use
of nanotechnology to medicine and healthcare. It has been utilised to treat cancer and
cardiovascular disease, two of the most prevalent diseases. Without realising it, we use things
made possible by nanotechnology on a daily basis. Science, engineering, and technology applied
to the nanoscale is called nanotechnology. Nanotechnology is helping to considerably improve,
even revolutionize, many technology and industry sectors: information technology, homeland
security, medicine, transportation, energy, food safety, and environmental science, among many
others. In almost every field Nanotechnology’s are used. Further, these systems can deliver drug
to specific tissues and provide controlled release therapy. This targeted and sustained drug
delivery decreases the drug related toxicity and increase patient’s compliance with less frequent
dosing. Nanotechnology has proven beneficial in the treatment of cancer, AIDS and many other
disease, also providing advancement in diagnostic testing. Numerous business and technological
areas, including information technology, homeland security, healthcare, energy, transportation,
food safety, and environmental research, are greatly benefiting from nanotechnology, which is
even revolutionising some of them. By delivering the medication in a targeted and sustained
manner, the toxicity associated with the treatment is reduced, and patients comply with fewer
doses. Through the manipulation of size, surface characteristics and material used, the
nanoparticles can be developed into smart systems, encasing therapeutic and imaging agents as
well as bearing stealth property.
Key Word: Nanotechnology, Nanoscale , Nanomedicine, Drug Delivery.
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Chapter I
Introduction
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[Introduction] [Chapter1]
1.1 What Is Nanotechnology
Nanotechnology is a mindset, even though the scientific community is fascinated with the field
of nanoscience, most of the ongoing discussions, definitions, and attention is focused on
nanotechnology. As such, it represents a broad term which demonstrates the apotheosis of man's
ceaseless urge for knowledge having practical potential. The meaning of the term
nanotechnology is any technology operating on the nanoscale which has applications in the real
world, that is, to employ single atoms and molecules to form functional structures .
The field of nanotechnology involves the creation and utilization of chemical, physical, and
biological systems with structural features between single atoms or molecules to submicron
dimensions, and also the assimilation of resultant nanostructures into larger systems.Nanoscience
is the study of the unique properties of materials between 1-100 nm, and nanotechnology is the
application of such research to create or modify novel objects. The ability to manipulate
structures at the atomic scale allows for the creation of nanomaterials. Nanomaterials have
unique optical, electrical and/or magnetic properties at the nanoscale, and these can be used in
the fields of electronics and medicine, amongst other scenarios. Nanomaterials are unique as they
provide a large surface area to volume ratio. Unlike other large-scaled engineered objects and
systems, nanomaterials are governed by the laws of quantum mechanics instead of the classical
laws of physics and chemistry. In short, nanotechnology is the engineering of useful objects and
functional systems at the molecular or atomic scale [1]. Nanomedicine is the term used to refer to
the applications of nanotechnologies in medicine and healthcare. Specifically, nanomedicine uses
technologies at the nanoscale and nano-enabled techniques to prevent, diagnose, monitor and
treat diseases [2].Nanotechnologies exhibit significant potential in the field of medicine,
including in imaging techniques and diagnostic tools, drug delivery systems, tissue-engineered
constructs, implants and pharmaceutical therapeutics[3] and has advanced treatments of several
diseases, including cardiovascular diseases, cancer, musculoskeletal conditions, psychiatric and
neurodegenerative diseases, bacterial and viral infections, and diabetes. Nanotechnologies have
had a significant impact in almost all industries and areas of society as it offers i) better built, ii)
safer and cleaner, iii) longer-lasting and iv) smarter products for medicine, communications,
everyday life, agriculture and other industries[4].The use of nanomaterials in everyday products
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can be generally divided into two types. First, nanomaterials can be merged or added to a pre-
existing product and improve the composite objects' overall performance by lending some of its
unique properties. Otherwise, nanomaterials such as nanocrystals and nanoparticles can be used
directly to create advanced and powerful devices attributed to their distinctive properties. a pre-
existing product and provide some of its special qualities to enhance the composite products'
overall performance. Otherwise, because to their unique features, nanomaterials like
nanoparticles and nanocrystals can be employed directly to produce sophisticated and potent
devices. The benefits of nanomaterials could potentially affect the future of nearly all industrial
sector.
1.2 History of nanotechnology

The history of nanotechnology traces the development of the concepts and experimental work
falling under the broad category of nanotechnology. Even though nanotechnology seems like a
budding aspect of science, its utilization by humanity isn't novel at all. The history of
nanomaterials usage in construction dates back to 4500 years ago when natural asbestos
nanofibres were utilized for ceramic matrices. [5]One of the oldest, richest, and progressive
cultures globally, Egyptians, realized the capabilities of nanomaterials 4000 years ago. The
historical trajectory of nanomaterials and nanotechnology prior to the millennium.Although the
field of nanotechnology is relatively new, its fundamental ideas have been developed over a
longer time span in scientific study. [6]The convergence of scientific advancements, including
the development of the scanning tunnelling microscope in 1981 and the discovery of fullerenes
in 1985, led to the emergence of nanotechnology in the 1980s. The book Engines of Creation,
published in 1986, provided a conceptual framework for the objectives of nanotechnology and
helped to popularise it. In the early 2000s, the field saw an increase in public recognition and
controversy, with notable discussions about its possible ramifications as well as the viability of
the applications its proponents had in mind of molecular nanotechnology, and as governments
take steps to encourage and provide funding for nanotechnology research.
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The first commercial uses of nanotechnology also appeared in the early 2000s [7], although they
were restricted to the large-scale uses of nanomaterials rather than the revolutionary uses that the
field had in mind.
Nearly every developed country launched nanotechnology programmes in the late 1990s and
early 2000s, which sparked a global upsurge in nanotechnology-related activity. An Interagency
Working Group on Nanotechnology (IWGN) was formed in the United States by the Office of
Science and Technology Policy (OSTP) and includes officials from the U.S. Air Force, U.S.
Navy, and NASA, among other government agencies. The U.S. National Nanotechnology
Initiative (NNI) was established by the IWGN in collaboration with industry and academics. The
Canadian institutions include the NanoQuebec consortium, the National Institute of
Nanotechnology (NINT) in Alberta, and five (5) National Research Council research institutes in
Ontario.IBM achieved a major achievement in 1990 when a team of scientists formed the letters
"IBM" out of 35 distinct xenon atoms. Another breakthrough surfaced. beginning in 1985 with
the identification of new forms for carbon atoms. These novel forms—called buckyballs—are
circular molecules composed of sixty carbon atoms. As a result, in 1991, an analogous chemical
form called the carbon nanotube was discovered. Given that they weigh only a sixth of the
weight of steel and are around 100 times stronger, carbon nanotubes remain one of the most
potential applications of nanotechnology. They have possess peculiar heat and conductivity
properties. Simultaneously, research on semiconductor nanocrystals produced quantum dots,
which have characteristics in between those of discrete molecules and bulk semiconductors.
The worldwide micro-nanotechnology cluster Minalogic in Grenoble, the Systematic cluster in

the Paris region, and the SCS cluster in Sophia Antipolis are among the activities conducted in
France. The German government's Nano-initiative is one of the programmes in the country. It
consists of the following: NanoFab for the electronics industry; NanoMobil for the automotive
industry; NanoLux for the optical industry; Nano for Life for the life science industries; and
Nano in Production for the production of nanomaterials. MEXT (Ministry of Education, Culture,
Sports, Science and Technology) and METI (Ministry of Economy, Trade and Industry) have
been in charge of activities in Japan. Among their many projects is the creation of the
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Nanotechnology Researchers Network. Through the network, general researchers across Japan
can access advanced and large-scale equipment owned by public organisations and certain
universities, like high-voltage electron microscopes and nanofabrication facilities, supporting the
research on nanotechnology conducted by universities and private organisations. In order to
produce practical devices and procedures and provide economic advantages, research on
nanoscale characteristics, material synthesis and characterization, and application development
remain the main areas of attention for scientists worldwide. The significance of addressing the
safety and health implications of nanomaterials as well as teaching upcoming scientists and
engineers about this developing topic is becoming increasingly apparent.
1.3 Nanoparticles
Polymeric particles made of synthetic or natural polymers, known as nanoparticles, are spherical
in shape. Their sizes vary from 10 to 500 nm. These particles offer a wide variety of possible
uses due to their spherical form and excellent surface area to volume ratio (Berry & Curtis,
2003). Rapid advancements in nanoparticle technology have made it possible to treat a wide
range of illnesses, including neurological conditions like Parkinson's and Alzheimer's (Emerich
& Thanos, 2003). Nevertheless, because of the blood-brain barrier's (BBB) limitations,
efficiently and locally delivering medications to the brain continues to be difficult. This barrier,
which is mostly made up of endothelial cells connected by tight junctions in their outer
membranes, restricts the movement of molecules across it by limiting molecular exchange to
transcellular transport. Although a variety of diseases, such as hypertension and allergic
encephalomyelitis, have been demonstrated to enhance BBB permeability to nanoparticles, the
healthy BBB also substantially shields the brain from exposure to blood-borne nanoparticles.NPs
are particles that are smaller than bulk material, with sizes ranging from 1 to 100 nm. Because of
its special qualities, the production of nanoscale materials—metallic nanoparticles, in
particular—has attracted a lot of interest in the past 10 years [4]. Natural describes a component
of the process as well as the type of materials employed. [9].
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1.4 Properties of nanoparticles
Among their many projects is the creation of the Nanotechnology Researchers Network.
Through the network, general researchers across Japan can access advanced and large-scale
equipment owned by public organisations and certain universities, like high-voltage electron
microscopes and nanofabrication facilities, supporting the research on nanotechnology conducted
by universities and private organisations. In order to produce practical devices and procedures
and provide economic advantages, research on nanoscale characteristics, material synthesis and
characterization, and application development remain the main areas of attention for scientists
worldwide. The significance of addressing the safety and health implications of nanomaterials as
well as teaching upcoming scientists and engineers about this developing topic is becoming
increasingly apparent. with the previously designated range of 1 to 1,000 nm, often known as the
mesoscale and occasionally associated with the area of colloid science. Consequently, it is not
unusual to come across material that uses the words "nanoparticles" and "colloidal particles"
interchangeably. When it comes to particles smaller than 100 nm, the distinction is basically
conceptual.[10] Based on their size, shape, and composition, nanoparticles may be categorised
into a wide range of categories. Certain classifications make a distinction between inorganic and
organic nanoparticles; fullerenes, quantum dots, and gold nanoparticles belong to the latter
category, while dendrimers, liposomes, and polymeric nanoparticles belong to the former.
Different categories separate nanoparticles based on their composition, such as carbon-based,
ceramic, semiconducting, or polymeric. Furthermore, nanoparticles can be categorised as soft
(such as liposomes, vesicles, and nanodroplets) or hard (such as titania [titanium dioxide], silica
[silica dioxide] particles, and fullerenes)[11]. The classification of nanoparticles is usually based
on how they are used, as in fundamental research vs diagnosis or therapy, or it may have
something to do with how they were made.
Three primary physical characteristics of nanoparticles are as follows: (1) they are very mobile in
their free state (for example, a 10-nm-diameter silica nanosphere will sediment in water at a rate
of 0.01 mm/day under gravity if no external influence is present); (2) they have large specific
surface areas (for example, a standard teaspoon, or about 6 ml, of 10-nm-diameter silica
nanospheres has more surface area than a dozen doubles-sized tennis courts combined; 20% of
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all the atoms in each nanosphere will be at the surface); and (3) they may display what are
known as quantum effects. Consequently, depending on the product or usage, nanoparticle
composition might vary greatly.[12]
1.5. Types of nanoparticles
To date, several nanoparticles and nanomaterials have been investigated and approved for
clinical use. Some common types of nanoparticles are discussed below.
1.5.1. Micelles
Amphiphilic molecules and lipids combine to form micelles, which are amphiphilic surfactant
molecules. Micelles can be utilised to integrate hydrophobic therapeutic medicines because they
spontaneously aggregate and self-assemble into spherical vesicles under aqueous circumstances,
with a hydrophilic outer monolayer and a hydrophobic core. Micelles' special qualities enable
hydrophobic medicines to dissolve more readily, increasing their bioavailability. Micelles have a
diameter of 10–100 nm. Micelles are used as therapeutic agents, imaging agents, drug delivery
agents, and contrast agents.[13]
1.5.2. Liposomes
Liposomes are spherical vesicles made of lipid bilayers that range in size from 30 nm to several
microns. Hydrophilic therapeutic compounds can be incorporated into the liposomal membrane
layer of liposomes, whereas hydrophobic agents can be incorporated into the aqueous phase.
Because liposomes may have their surface features changed by adding polymers, antibodies, or
proteins, liposomes can be used to include macromolecular medications such solid metals and
nucleic acids. The first FDA-approved nanomedicine for the treatment of breast cancer is
poly(ethylene glycol) (PEG)ylated liposomal doxorubicin (Doxil), which increases the effective
drug concentration in malignant effusions without requiring an increase in the total dosage.[14]
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1.5.3.Microemulsions
Microemulsions are isotropic, thermodynamically stable systems composed of oil, water, and
surfactant. Thermodynamic stability rather than size, is the defining hallmark of a
microemulsion, although the droplet sizes are still below 100 nm (and many times much smaller)
Be that as it may, what is critical about microemulsions is that, they contain two phases
consisting of two immiscible liquids that are mixed together and stabilized with the aid of a
surfactant with or without a co-surfactant. They may have droplets in the range of 5–100 nm.
The difference between microemulsions and emulsions is that, the later are opaque mixtures of
two immiscible liquids, thermodynamically unstable and usually require the application of high
torque mechanical mixing or homogenization to produce dispersed droplets in the range of 0.2–
25 mm. Both types can be made as water-in-oil (w/o) or oil-in-water (o/w)[15]. Therefore,
stabilisation against Ostwald ripening is very important because the resulting change in droplet
size could lead to a loss of physical stability of the dosage form. Microemulsion instability can
cause Oswald ripening, which can cause the small droplets to dissolve and the large droplets to
grow in size. Microemulsion stability is determined by the components used [16]. Choosing
components needs to take safety into account as well as other crucial factors.
1.5.4. Dendrimers
Dendrimers are macromolecules made up of external functional groups and branching repeating
units that extend from a central core. These functional groups, which can be anionic, neutral, or
cationic terminals, can change the structure's overall composition as well as its chemical and
physical characteristics. Dendrimers are extremely bioavailable and biodegradable because
therapeutic substances can be enclosed inside the inner space of dendrimers or linked to the
surface groups[17]. It has been demonstrated that dendrimer conjugates containing saccharides
or peptides have better antibacterial, antiprion, and antiviral qualities as well as increased
solubility and stability when therapeutic medications are absorbed. Dendriplexes, or
polyamidoamine dendrimer-DNA complexes, have been studied as gene delivery vectors and
show potential for improving medication effectiveness, targeted drug administration, and
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successive gene expression. Because they may be transformed, dendrimers are a potential class
of particulate materials for use in biological applications including drug administration and
imaging.
1.5.5. Carbon nanotubes
Carbon nanotubes are spherical molecules made of sheets of carbon atoms wrapped up into a
single layer (graphene). They might consist of several concentrically connected nanotubes or be
single- or multi-walled nanotubes. Carbon nanotubes can reach remarkably high loading
capacities as drug carriers because of their large exterior surface area. Furthermore, carbon tubes
have shown to be attractive as biological sensors and imaging contrast agents due to their distinct
optical, mechanical, and electrical characteristics[18].
1.5.6. Metallic nanoparticles:
Gold and iron oxide are examples of metallic nanoparticles. Hydrophilic polymers like dextran
or PEG are combined with a magnetic core (4-5 nm) to form iron oxide nanoparticles. While
gold nanoparticles may be functionalized by adding a monolayer of surface moieties as ligands
for active targeting, gold nanoparticles are made up of a core of gold atoms surrounded by
negatively reactive groups on the surface. Metallic nanoparticles have been applied as optical
biosensors, drug delivery vehicles, imaging contrast agents, and laser-based therapy.
1.5.7. Quantum dots
Quantum dots (QDs) are fluorescent semiconductor nanocrystals that range in size from 1 to 100
nm. They have demonstrated promise for usage in a number of biological applications, including
cellular imaging and drug administration. The structure of quantum dots is shell-core, with the
periodic table's II-VI or III-V group elements commonly making up the core. Quantum dots are
unique in their optical characteristics and have been used in medical imaging due to their small
size, excellent brightness, and stability.
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1.6. Some natural polymers in nanodrug delivery

1.6.1. Starch
One typical polysaccharide is starch. It mostly happens in plants since they serve as materials for
storage. Chemically speaking, it is made up of repeating glycopyranose units in an alpha D-[1, 4]
bond, which when hydrolyzed, produces the monosaccharide glucose (Heller et al., 1990). Starch
is widely used in pharmaceutics. In controlled drug delivery, it is utilised as an excipient and co-
polymer [19], as drug carriers in scaffolds for tissue engineering [20], as hydrogels, and as
solubility enhancers. Makham studied the use of chitosan cross-linked starch polymers as
carriers for oral insulin delivery, adjusting the bio-adhesive and less adhesive qualities of
chitosan and carboxymethyl starch to create hydrogels loaded with insulin. Starch nanoparticles
have been used to deliver insulin via non-invasive routes. The authors however noted that,
Insulin delivered by this method however faces the challenge of being broken down by
proteases[21].
1.6.2. Chitosan
This polymer is obtained from the partial N-deacetylation of chitin found in the shells of
crustacean. It is composed of glucosamine and N-acetyl glucosamine linked by β 1-4 glucosidic
bonds and is one of the most widely studied natural polymers for nano-drug delivery. The
deacetylation of chitin is both concentration and temperature dependent with optimal yields
achieved at temperatures between 600C- 800C using 50%w/w alkali. Chitosan combination was
also used by Menon et al. [22] for therapeutic drug delivery. Polyoxometalates (POM) and
chitosan nanocomplexes were evaluated as anti-cancer preparations. Since POMs, despite their
toxicity, have demonstrated potential for use as anti-viral and anti-tumor agents, chitosan's
function was to reduce POM toxicity by altering its surface characteristics. Ionotropic gelation
was used to create monodispersed particles with a size of 200 nm. Probe sonication was shown
to be a more effective method of controlling particle size and dispersion than ultrasonication.
Research conducted in vitro demonstrated that the nano-complex required far fewer doses of
medication than the POM alone to maintain drug release with increased anti-tumor effectivenes
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1.6.3. Gelatin
Gelatin is obtained from the breakdown and hydrolysis of collagen, obtained from the connective
tissues, bones and skins of animals. It is a known matrixing agent drug delivery. Bajpai and
Shoubey [22] describes a process for the controlled release of sulphamethoxazole using 2
different gelatin nano-particles {Type A (porcine skin) and type B gelatin( bovine skin)} and
cross linked with gluteraldehyde; Nano-particles of varying gelatin concentrations were prepared
by solvent evaporation techniques and drug release kinetics evaluated using appropriate kinetic
models. Gene therapy also makes use of proteins as nano carriers. Since the injection of naked
DNA into live tissue results in enzymatic destruction and limited cellular uptake because of
repulsion between the negatively charged DNA and cell membrane, both viral and non-viral
vectors are utilised for the transfection of DNA into cells. In order to explore the potential of
avidin-modified gelatin nanoparticles for the administration of biotinylated PNA (Peptide nucleic
acids) as an anti-sense treatment, Coester et al. [24] employed this technique.
1.6.4. Hydroxyapatite-Based Nanoparticles
Hydroxyapatite (HAp) has great applications in the biomedical field and is considered the best
option in the pharmaceutical field due to its excellent bioactivity and biocompatibility.
Hydroxyapatite is derived from the mineral compounds of human bones, teeth, and hard tissues.
The basic units of HAp are calcium and phosphates (CaP) characterized as
M14M26(PO4)6(OH)2, in which M1 and M2 are two crystallographic arrangements. The stability
of CaP is directly related to the presence of water molecules during synthesis and the medium
where it was applied. HAp powder was synthsized using a hydrothermal method with the use of
calcium nitrate [Ca(NO3)2.4H2O] for calcium and potassium dihydrogen phosphate
[(NH4)2HPO4] and phosphorous, and it was used as a precursor..
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Chapter II
Literature Review Of Nanotechnoloy
Page 21
[Literature Review Of Nanotechnology] [Chapter2]
2. Review Of The Literature

2.1.The research paper titled "Nanotechnology-based drug delivery systems and herbal
medicines: a review" explores the intersection of nanotechnology and herbal medicine in drug
delivery systems. Published in the International Journal of Nanomedicine in 2014, the paper
provides an overview of how nanotechnology can enhance the efficacy and delivery of herbal
medicines.
Key points discussed in the paper include:
The paper introduces nanotechnology as a promising field for improving drug delivery
systems. Nanoparticles have unique properties that make them suitable for targeted drug
delivery, controlled release, and enhanced bioavailability.
It highlights the growing interest in herbal medicines due to their perceived safety and
efficacy compared to synthetic drugs. However, challenges such as poor solubility, low
bioavailability, and lack of targeted delivery hinder their full potential.
The paper explores various nanotechnology-based approaches employed to overcome the

limitations of herbal medicines. This includes nanoemulsions, nanosuspensions, solid lipid
nanoparticles, polymeric nanoparticles, liposomes, and micelles.
Nanotechnology offers several advantages, such as improved solubility, enhanced stability,

controlled release, targeted delivery to specific tissues or cells, reduced toxicity, and
increased therapeutic efficacy.The paper discusses specific examples and case studies where
nanotechnology has been successfully applied to deliver herbal medicines. This includes the
use of nanocarriers to deliver curcumin, resveratrol, silymarin, and other herbal compounds.
Despite the promising potential, the paper also highlights challenges and limitations in the
application of nanotechnology to herbal medicine, such as scalability, regulatory hurdles,
andsafety concerns. The authors suggest future research directions to address these
challenges and further optimize nanotechnology-based drug delivery systems for herbal
medicines.
Page 22
Overall, the paper provides a comprehensive review of the current state of nanotechnology-
based drug delivery systems for herbal medicines, highlighting opportunities and challenges in
this emerging field
2.2. The paper titled "Emerging Applications of Nanotechnology in Healthcare Systems: Grand
Challenges and Perspectives," published in Pharmaceuticals in 2021, provides an extensive
overview of the current state, challenges, and future perspectives of nanotechnology applications
in healthcare.
Here's a summary of the key points discussed in the paper:
The paper begins by introducing nanotechnology and its significance in revolutionizing

healthcare systems. Nanotechnology offers promising solutions for drug delivery, diagnostics,
imaging, regenerative medicine, and therapeutics. One of the primary applications discussed is
the use of nanoparticles for drug delivery. Nanoparticles provide targeted delivery, enhanced
bioavailability, prolonged circulation time, and reduced side effects compared to conventional
drug delivery methods. Nanotechnology plays a crucial role in the development of advanced
diagnostic tools, including biosensors, imaging agents, and point-of-care devices. These
nanodiagnostic platforms offer high sensitivity, specificity, and rapid detection of diseases.
The paper highlights the significant impact of nanotechnology in cancer therapy. Nanoparticles
can selectively target cancer cells, deliver therapeutic agents, and overcome multidrug resistance,
leading to improved treatment outcomes.Despite the promising potential, the authors discuss
several challenges and limitations associated with nanotechnology in healthcare. These include
toxicity concerns, regulatory hurdles, scalability issues, and the need for interdisciplinary
collaboration.The paper outlines future perspectives and potential directions for nanotechnology
in healthcare. This includes the development of personalized nanomedicine, integration with
artificial intelligence and machine learning, addressing ethical and safety concerns, and
promoting global collaboration. The authors conclude by emphasizing the transformative impact
of nanotechnology on healthcare systems and the need for concerted efforts to address challenges
and realize its full potential in improving patient care and public health.
Page 23
2.3. The paper titled "Nanotechnology: From In Vivo Imaging System to Controlled Drug
Delivery," published in Nanoscale Research Letters in 2017, provides a comprehensive overview
of the multifaceted applications of nanotechnology in healthcare, focusing on in vivo imaging
systems and controlled drug delivery.
The paper introduces nanotechnology as a transformative field with diverse applications in

medicine, particularly in imaging and drug delivery.
It discusses the role of nanotechnology in developing advanced in vivo imaging systems for
diagnostic purposes. Nanoparticles, such as quantum dots, iron oxide nanoparticles, and gold
nanoparticles, are highlighted for their ability to improve imaging contrast and sensitivity,
enabling early detection and monitoring of diseases.
The paper explores how nanotechnology enables precise and controlled drug delivery.
Nanoparticles can be engineered to target specific tissues or cells, release drugs in a sustained
manner, and overcome biological barriers such as the blood-brain barrier.
Despite the promising potential, the paper discusses challenges such as biocompatibility,
scalability, and regulatory approval. The authors emphasize the importance of
interdisciplinary collaboration and further research to address these challenges and advance
the field of nanomedicine.The paper concludes by underscoring the transformative role of
nanotechnology in healthcare, from enhancing in vivo imaging systems to enabling
controlled drug delivery. Nanotechnology holds great promise for improving diagnostics,
therapeutics, and patient outcomes in various medical conditions
Page 24
2.4. The paper titled "Nanotechnology in Drug Delivery: Present Status and a Glimpse into the
Future," authored by Banerjee and published in Therapeutic Delivery in 2018, provides a
succinct overview of the current state and future prospects of nanotechnology in drug delivery.
The author briefly outlines the existing applications of nanotechnology in drug delivery,
highlighting its potential to enhance drug solubility, bioavailability, and targeting, while
minimizing side effects.Banerjee acknowledges the challenges faced in the field of
nanotechnology, such as issues related to toxicity, scalability, and regulatory approval.
However, the author also emphasizes the significant opportunities presented by
nanotechnology, particularly in addressing unmet medical needs and advancing personalized
medicine. The paper provides a glimpse into the future of nanotechnology in drug delivery,
suggesting potential advancements such as the development of multifunctional nanoparticles,
smart drug delivery systems capable of responding to physiological cues, and the integration
of nanotechnology with other emerging technologies like artificial intelligence and gene
editing. Banerjee concludes by underscoring the importance of continued research and
innovation in nanotechnology to overcome existing challenges and unlock its full potential in
revolutionizing drug delivery systems for improved patient outcomes.
Overall, the paper offers a concise overview of the present status and future directions of
nanotechnology in drug delivery, highlighting both the challenges and opportunities in the field.
2.5. The research paper titled "Nanotechnology: A Novel Approach for Drug Development in
Health Care System," authored by Sahoo et al. and published in Current Nanomaterials in 2020,
explores the potential of nanotechnology as a novel approach for drug development in
healthcare.
The paper provides an overview of how nanotechnology is being increasingly utilized in the
development of pharmaceuticals, offering several advantages such as improved drug delivery,
enhanced bioavailability, and targeted therapy. Various nanomaterials and nanocarriers are
Page 25
discussed for their applications in drug delivery systems, including liposomes, nanoparticles,
dendrimers, and nanogels.Furthermore, the authors delve into the specific ways nanotechnology
is transforming healthcare, particularly in the treatment of diseases like cancer, cardiovascular
disorders, infectious diseases, and neurological conditions. Nanoparticles are shown to play a
crucial role in delivering therapeutic agents to targeted sites in the body, thereby minimizing side
effects and improving treatment outcomes.
The paper also addresses challenges associated with nanotechnology in drug development, such
as safety concerns, regulatory issues, and scalability. Despite these challenges, the authors
highlight the immense potential of nanotechnology to revolutionize drug delivery and therapy,
paving the way for more effective and personalized healthcare solutions.
Overall, the paper underscores the significance of nanotechnology as a promising approach in

drug development, offering insights into its current applications, challenges, and future prospects
in healthcare.
2.6. The paper titled "Impact of Nanotechnology on Drug Delivery," authored by Omid C.
Farokhzad and Robert Langer, and published in ACS Nano in 2009, examines the significant
influence of nanotechnology on drug delivery.
The authors highlight how nanotechnology has revolutionized drug delivery by offering
innovative approaches to overcome traditional limitations. Nanoparticles, such as liposomes,
polymeric nanoparticles, dendrimers, and nanotubes, are discussed for their ability to improve
drug solubility, bioavailability, and targeted delivery to specific sites within the body. The paper
emphasizes the transformative impact of nanotechnology in enhancing therapeutic efficacy while
minimizing side effects. Through precise control over particle size, shape, and surface properties,
nanoparticles enable controlled release of therapeutic agents and enhanced cellular uptake,
leading to improved treatment outcomes.
Furthermore, the authors explore the potential applications of nanotechnology in various fields,
including cancer therapy, infectious diseases, neurological disorders, and cardiovascular
Page 26
conditions. Nanoparticles offer opportunities for personalized medicine and tailored treatment
strategies by delivering drugs directly to diseased tissues while sparing healthy cells.
Despite the promising advancements, the paper also addresses challenges associated with
nanotechnology in drug delivery, such as concerns regarding toxicity, biocompatibility, and
regulatory approval. However, the authors remain optimistic about the continued progress and
future potential of nanotechnology to revolutionize drug delivery and improve patient care.
Overall, the paper provides valuable insights into the transformative impact of nanotechnology
on drug delivery, highlighting its potential to advance therapeutic strategies and address unmet
medical needs in various healthcare settings. It discusses the potential of nanotechnology in
overcoming limitations of conventional drug delivery methods, highlighting opportunities for
targeted drug delivery, enhanced efficacy, and reduced side effects. The chapter also addresses
challenges such as biocompatibility, scalability, and regulatory hurdles associated with the
development and implementation of nanotechnology-based drug delivery systems.
Overall, the chapter offers valuable insights into the current state of nanotechnology in drug
delivery and outlines future directions for research and development in this field
2.7. The book "Emerging Nanotechnologies for Diagnostics, Drug Delivery, and Medical
Devices," edited by Mitra, Cholkar, and Mandal in 2017, provides a comprehensive overview of
the applications of nanotechnology in healthcare.
It covers emerging nanotechnologies in diagnostics, drug delivery systems, and medical devices,
offering insights into how nanotechnology is transforming these fields. The book explores the
use of nanoparticles, nanocarriers, and nanoscale materials in improving diagnosis, drug delivery
efficiency, and the development of advanced medical devices.Overall, it serves as a valuable
resource for researchers, practitioners, and students interested in understanding the potential of
nanotechnology in revolutionizing healthcare.
Page 27
The book chapter titled "Nanotechnology-Based Drug Delivery Systems: Challenges and
Opportunities," authored by Sharma et al. in 2018, provides a concise overview of the challenges
and opportunities in the field of nanotechnology-based drug delivery systems.
2.8. The research article titled "Nanotechnology Drug Delivery System: Tools in Advanced
Pharmaceutical & Human Healthcare," authored by Hasan et al. in 2016, provides an overview
of the applications of nanotechnology in drug delivery and its implications for pharmaceutical
and human healthcare.The article discusses the potential of nanotechnology-based drug delivery
systems to improve drug solubility, bioavailability, and targeting. It highlights various
nanocarriers and nanoscale materials used in drug delivery, emphasizing their role in enhancing
therapeutic efficacy and reducing side effects. Furthermore, the article addresses the importance
of interdisciplinary collaboration and regulatory considerations in the development and
implementation of nanotechnology-based drug delivery systems.Overall, the article underscores
the significance of nanotechnology as a tool for advancing pharmaceuticals and human
healthcare, offering insights into its potential applications and future directions.
2.9.Calixto, G. M. F., Bernegossi, J., De Freitas, L. M., Fontana, C. R., & Chorilli, M. (2016).
Nanotechnology-based drug delivery systems for photodynamic therapy of cancer: a review.
Molecules, 21(3), 342.
The review explores the potential of nanotechnology-based drug delivery systems for enhancing
photodynamic therapy (PDT) in cancer treatment. Photodynamic therapy involves using
photosensitizing agents activated by light to selectively destroy cancer cells. Nanotechnology
offers promising strategies to improve PDT efficacy by enhancing drug delivery, targeting
specific cancer cells, and minimizing side effects. The review discusses various nanocarriers,
including liposomes, polymeric nanoparticles, dendrimers, and carbon-based nanomaterials,
highlighting their advantages in PDT applications. It also covers recent advancements in
nanotechnology-driven PDT approaches, such as targeted delivery systems, combination
therapies, and theranostic platforms. Overall, the review underscores the potential of
nanotechnology in revolutionizing PDT for more effective cancer treatment
Page 28
3.1.Preparation of nanoparticles
3.1.1.Nanosuspensions
Nanosuspension refers to production of sub-micron-sized particles by subjecting the combination

of drug and a suitable emulsifier to the process of milling or high-pressure homogenization.
Particles produced by traditional milling and precipitation techniques often have diameters
substantially larger than 1 mm. Therefore, selecting the manufacturing process to guarantee the
creation of sub-micron particles is an essential stage in the preparation of the nanosuspension.
Drugs that dissolve poorly can be made more soluble by using formulations in the form of
nanosuspensions. Many of the novel drug candidates that come out of drug discovery
programmes are poorly bioavailable due to their insoluble nature in water, which causes
development attempts to be shelved. By forming them into crystalline nanosuspensions, they
may now be saved. For the production of nanosuspensions, commercial methods including media
milling and high-pressure homogenization have been employed. Because of their specific
qualities, nanosuspensions may now be used in a wide range of dosage forms, including ones
that need specialised delivery methods like mucoadhesive hydrogels.[25] There are several ways
to administer nanosuspensions, including parenteral, oral, ophthalmic, and pulmonary. At the
moment, efforts are focused on expanding their use in medication administration that is site-
specific. Spironolactone, a model medication with limited solubility, has been prepared in
several particle sizes to produce micro- and nanosuspensions of the solid lipid nanoparticle and
DissoCube types. The bioavailability of the DissoCubes nanosuspension was significantly
improved. The increase in bioavailability is not primarily determined by the reduction of particle
size.
3.1.2. Necessity for nanoparticle-based drug formulations
There are various reasons why using nanoparticles for therapeutic and diagnostic agents, as well
as advancement of drug delivery, is important and much needed.
 A more inventive kind of carrier system is needed for products comprising proteins or
nucleic acids in order to increase their effectiveness and shield them from unintended
breakdown. Notably, particle size directly affects the majority of drug delivery
Page 29
modalities' efficiency (with the exception of intravenous and solution). Drug
nanoparticles have greater bioavailability and increased solubility due to their vast
surface area and tiny size. They also have the capacity to pass past the tight connections
of skin endothelial cells, enter the pulmonary system, and cross the blood brain barrier
(BBB). Nanoparticles composed of both synthetic and natural polymers—biodegradable
and non-biodegradable—have drawn increased interest because of their capacity to be
tailored for drug administration that is targeted, enhanced bioavailability, and controlled
release of medicine from a single source.
 Another benefit for pharmaceutical sales to diversify is the creation of novel medication
delivery methods. Pharmaceutical firms are developing new formulations of their existing
medications due to innovative drug delivery. Although the patients will benefit from
these novel formulations, they will also generate a strong market force that will propel
the creation of ever more efficient delivery systems.
 Nanomedicine uses technologies at the nanoscale and nano-enabled techniques to
prevent, diagnose, monitor and treat diseases. • Nanotechnologies have shown great
promise in the medical field, particularly in the areas of drug delivery, tissue engineering,
implants, psychiatric and neurological disorders, diabetes, and musculoskeletal disorders.
They have also improved the treatment of a number of diseases, including cancer,
cardiovascular disease, musculoskeletal disorders, bacterial and viral infections, and
musculoskeletal disorders[27].
Page 30
3.1. Mechanism of Nanoparticles’ Brain Drug Delivery (across BBB)
The NPs are commonly administered via intranasal, intraventricular, intraparenchymal routes.
All these routes enabled nanoparticles to cross the BBB due to their small size. Several systems,
including receptor-mediated processes, active transport, and passive transport, are employed to
distribute nanoparticles into the brain once they cross the blood-brain barrier (BBB).[28]
Because of their tiny size, nanoparticles may passively diffuse through the blood-brain barrier's
endothelial cells, engage favourably with brain receptors, and recognise ligands for interaction.
A number of possible paths for the transport processes across the BBB have been suggested., as
illustrated in Fig. 1.
Fig 1:Mechanism of nanopartticles across BBB
This mechanism is highly dependent on drugs` physicochemical characteristics such as

molecular weight (less than 400Da); lipophilicity – log Po/w between 5–6, or log D value
Page 31
between 0 and 3 (the latter also includes the partition of ionized forms at pH 7.4); hydrogen
bonds (the cumulative number usually < 8), polar surface area (< 60–70 Å2), molecular shape
(i.e., spherical molecules without branching permeate easily), charge (positive)[29]
Drug administration via nanoparticles can also make use of this transport mechanism provided
the carriers are appropriately conjugated with certain ligands[30]. The receptors for insulin, low-
density lipoprotein (LDL), lactoferrin, transferrin, and leptin are among the most often targeted
(Fang et al. 2017). The procedure includes many steps: the ligand and the appropriate receptor
bind to produce an endocytotic vesicle, which is then internalised by endothelial cells and
exocytosed into the brain parenchyma.
3.2. Advantages and Disadvantages of Nanomedicines
When employed for brain illnesses, nanomedicines have both benefits and drawbacks .One of the
biggest advantages of nanomedicine is its ability to deliver drugs and other therapeutic agents
directly to the site of the disease. This precision medicine approach reduces the risk of side
effects and maximizes the therapeutic effect of the drug. Nanotechnology-based imaging
techniques, such as magnetic resonance imaging (MRI) and computed tomography (CT) scans,
allow for earlier and more accurate diagnosis of diseases, such as cancer. Nanoparticles can be
engineered to target specific cells or tissues in the body, which is particularly useful in cancer
therapy. This targeted therapy approach reduces the risk of damage to healthy cells and tissues
The use of nanoparticles in medicine is still a relatively new field, and there is limited knowledge
on their long-term toxicity. Studies have shown that some nanoparticles can accumulate in the
body and cause damage to organs and tissues. The development and production of nanoparticles
can be expensive, which could limit their availability and affordability. The use of nanomedicine
in humans is subject to strict regulatory approval, which can slow down the development and
implementation of new therapies.
Table 1: Advantages and disadvantages of nanomedicine.
Page 32
Nanomedicine Names Advantages Disadvantages Ref
Tacrine -loaded polymeric NPs are reserved in the brain Slowly degradable, [31]
NPs for long time, biocompatible, sometimes uncertain
low in cost, control drug toxicity
release, and targeted
conjugation with ligands
Rivastigmine -loaded They increase drug Increase oxidative stress, [31]

polymeric NPs concentration in the brain, toxicity
avoid phagocytosis by RES
Piperine -loaded SLNPs Widely examined, fewer side Low loading capacity, [32]
effects of drugs, improved easily cleared by
therapeutic effects and drug reticuloendothelial
solubility system
Folic-acid -loaded Highly biocompatible and Difficulty in binding with [33]

liposomes biodegradable, lipids, low stability and
High stability and drug carriage rate
bioavailability,
active surface targeted
Beta-Asarone -loaded Improved bioavailability, Thermodynamically

nanoemulsions capability to hydrolyze unstable, [33]
hydrophobic and hydrophilic instant drug release
drugs
Page 33
Chapter IV
Role in Nanocarriers In Major Types Of Cancer
Page 34
[Role Of Nanocarriers In Major Types Of Cancer [Chapter4]
4. Nanocarriers Role in Major Cancers

4.1 Brain Cancer
Brain malignancy is the most critical disease in the sense of treatment [34]. Malignancies of the
brain are most difficult to treat due to limits imposed by the blood–brain barrier . The BBB
contains the brain microvascular endothelium, which forms barriers to separate blood from the
brain's neuronal structures.The blood-brain barrier (BBB) keeps dangerous poisons, foreign
substances, and other metabolites out of the brain. Gliomas and glioblastomas are the dominant
group of brain malignancies. These two represent some of the worst types of brain cancer. 5.26
cases per 100,000 persons, or 17,000 new diagnoses, are reported annually. Chemotherapy and
radiation therapy are the most popular forms of treatment; temozolomide (TMZ) is typically used
in these procedures. The tiny size of nanoparticles (nm), their ability to target specific tissues,
and their ease of crossing the blood-brain barrier make them very promising for treating brain
cancer [35] .
Table2 :Various nanoparticles involved in brain cancer treatment in recent era.
Drug Loaded Cancer

NP Name NP Types Model Action Ref
on NPs Type
Endocytosis
occurs. Cytotoxic
Glioma
activity increased
DOX-SL- Gold and glioma
Doxorubicin In vitro both on LN-229 [36]
GG AuNPs nanoparticles stem cell
glioma cells and
lines
HNGC-2 glioma
stem cells.
Lapatinib- Constrain
Albumin- Murine
loaded Brain movement,
bound Lapatinib model [37,38]
human metastasis invasion and
nanoparticle in vitro
serum adhesion of high
Page 35
albumin brain-metastatic
4T1 cells.
Both LTNPs (10
mg kg−1) and
Lapatinib-
Lipoprotein- In vivo LTNPs (30 mg
incorporated
like Lapatinib Glioma murine kg−1) significantly [39]
lipoprotein
nanoparticles model constrain the
like NPs
progress of U87
xenografts.
Comparatively
greater
Gold–iron Cytotoxi
Curcumin– cytotoxicity
oxide Brain city and
lipoic acid Glutathione against cancerous [40]
nanocompos cancer apoptosi
conjugate U87MG cells
ites s assay
than standard
astrocyte cells.
Synergistic
Tocopherol Enhance influence of
polyethylene Fabricated cellular nanoparticles has
glycol synergistic Brain uptake increased the
Docetaxel [40]
chitosan bioadhesive cancer and delivery of
nanoparticle nanoparticles cytotoxi docetaxel into
s city brain melanoma
cells.
Chitosan or Methotrexate- Nanoparticles
Cytotoxi
glycol loaded show cytotoxicity
city
chitosan chitosan and Methotrexate C6 glioma against C6 cells
assay [40]
(GCS) glycol (MTX) cells line and are able
and cell
nanoparticle chitosan- to control
lines
s (NPs) based MDCKII-MDR1
Page 36
nanoparticles cell hindrance.
4.2 Breast Cancer
Cancer causes major deaths all over the world. Tumors spread due to the proliferation of cells
which invade through the lymphatic system to various parts of the body if they becomes
malignant .According to WHO, the ratio of deaths globally due to cancer is assessed to be 13%,
attributing 8.2 million deaths every year .Breast cancer is the most recorded type of melanoma
present in only females, and its severity leads to mortality more often than lung cancer . In 2012,
estimated female breast cancer cases were 1.7 million, with 25% of deaths all over the world
[42]. In a recent study, a report published in the name of Global Cancer Statistics 2020:
GLOBOCAN estimates the incidence and mortality worldwide for 36 cancers in 185 countries
and provides an update on cancer internationally [43]. A reported estimate is 19.3 million new
cancer cases (18.1 million excluding non-melanoma skin cancer) and almost 10 million cancer
deaths (9.9 million without non-melanoma skin cancer) occurring in 2020 worldwide. Female
breast cancer has exceeded lung cancer as the most frequently diagnosed cancer, with an
estimated 2.3 million new cases (11.7%), followed by lung (11.4%), prostate (7.3%), colorectal
(10%), and stomach (5.6%) cancers Surgery, chemotherapy, radiation therapy, hormonal therapy,
and targeted therapy are all used to treat breast cancer effectively. On the other hand, interest in
using nanotechnology to treat breast cancer has grown recently. Medications are delivered to the
precise target spot using a variety of organic and inorganic nanocarriers. Nanocarriers facilitate
targeted drug distribution and increase the hydrophobicity of anticancer medications [43].While
inorganic nanocarriers like magnetic nanocarriers, quantum dots, and carbon nanotubes (CNTs)
are effective at treating cardiac disorders, organic nanocarriers like polymeric nanocarriers,
liposome nanocarriers, and solid lipid nanocarriers .
Page 37
Fig 2: Mechanism of Nanocarries In Breast Cancer
Schematic representation of mechanism of drug letrozol loaded on solid lipid nanoparticles

(SLNs) and folic acid coupled to SLNs. The whole carrier was delivered inside the animal rat
model to treat effects on breast cancer cell lines. Inside cytoplasm, biodegradation occurred, as
well as drug release and caspases’ activation inside nucleus, causing apoptosis.[44]
Page 38
4.3. Nanoparticles’ role in treatment of breast cancer.
Nanomateri
Drug Anim
al (Organic Material
Loaded al Disease Description Ref.
Nanomateri Used
with NPs Model
al)
Lactate
dehydrogenase
(LDH) and 3-(4,
5-
Dimethylthiazol-
2-yl)-2, 5-
In-
Folic-acid- diphenyltetrazoli
vitro
receptor- um bromide
Solid lipid Letrozol MCF-
targeted (MTT) assays to
nanoparticles (LTZ) 7 Breast cancer [45]
solid lipid check cell
(SLNPs) Folic acid cancer
nanoparticle membrane
cell
s damage.Caspase-
lines
3 activity and
TUNEL assays
were performed
to confirm
induced
apoptosis.
CURC- Curcumin-loaded
Curcumin– loaded SLNs 5–10 folds
Solid Lipid SLNs and more effectively
Doxorubici In-
nanoparticles doxorubicin Breast cancer than curcumin in [45]
n (DOX) vitro
(CURC- p- free form,
SLNs) glycoprotei increasing
n (Pgp) toxicity in Pgp-
Page 39
expressing triple
negative breast
cancer.
Anti-HER2-
conjugated O-
succinyl chitosan
doxorubicin
graft pluronic
Copolymer- –core-shell HER2-over-
Doxorubici In- F127 copolymer [46,47
magnetite chitosan express in
n (DOX) vitro nanoparticles are ]
nanoparticles nanoparticle breast cancer
effective for the
s
making of
anticancer drug
carriers.
Combination
remedy by
PEGylated
DMMA-P-
ε-poly-l- doxorubici
Polymeric In- MCF-7 breast DOX/LAP
lysine n and [48]
nanoparticles vitro cancer cell nanoparticles
polymeric lapatinib
constrains the
nanoparticle
solid tumors to
shrink
Gemcitabin
Gemcitabine-
e- In
Colloidal hydrochloride-
hydrochlori vitro
gold Human breast loaded gold
de (GEM)- (MDA
nanoparticles Gemcitabi cancer nanoparticles
loaded -MB- [49]
Iron-based ne adenocarcino developed using
colloidal 231)
metal ma gum acacia as a
gold cell
network polysaccharides-
nanoparticle line
based system.
s
Page 40
CCMNPs were
targeted
L-
precisely,
carnosine-
In amassed in lump,
coated
Magnetic L- vitro showing
magnetic Breast cancer [47]
nanoparticles carnosine In noteworthy
nanoparticle
vivo decrease in lump
s
mass size with no
(CCMNPs)
general
harmfulness.
4. 4. Lung Cancer
Fundamentally, inhalation is the function of the lungs. Alveoli, or gas exchange zones, and
airways, which carry air into and out of the lungs, make up the lung.The barrier between the
alveolar wall and the capillaries is somewhat frail in the gas exchange component, but the
airways are really quite strong barriers against particle entry.When exposed to environmental
damage, the alveoli's large surface area and deep air blood exchange make them less healthy.
Some lung diseases, such as lung cancer, may be caused by these damage [50]. A number of
nanoparticles are now being developed for respiratory applications with the goal of doing away
with the limitations of conventional medications.Numerous lung conditions, including asthma,
TB, emphysema, and cystic fybrosis and cancer.
Page 41
Table 4: Recent discovered nanoparticle’s role in lung cancer treatment.
Exposure Animal
Nanoparticles Description Used for Ref
Method Model
Poly (L-aspartic
acid co lactic Mouse DPPE co-polymer NPs
Intraperitoneal Lung
acid)/DPPE xenograft laden with doxorubicin [52]
injection melanoma
copolymer model (DOX)
nanoparticles
PBAE polymers that self-
assemble with DNA and
Poly (β-amino Mouse
Intratumoral evaluated for transfection Small cell
ester) nanoparticle xenograft [52]
injection effectiveness in the p53 lung cancer
(PBAE) model
mutant H446 SCLC cell
line
The receptor factor (EGF)
Lipid polymeric Intraperitoneal Lung
Mice was co-designed with [53]
nanoparticles injection carcinoma
cisplatin plus doxorubicin
Methoxy poly -poly
(ethylenimine)-poly(l-
Doxorubicin and
glutamate) copolymers Metastatic
cisplatin (CDDP) Pulmonary Mouse
were manufactured as a lung [54]
co-loaded administration model
transporter for the melanoma
nanoparticles
codelivery of DOX and
CDDP
PAA-ss-OA-modified Non-small
Redox-responsive Mouse
Subcutaneous Erlotinib (ETB)-loaded cell lung
plus pH-sensitive xenograft [55]
injection lipid nanoparticles (PAA- melanoma
nanoparticles model
ETB-NPs) were made (NSCLC)
Page 42
using the emulsification

and solvent evaporation
method
MSC as lung-melanoma-
targeted drug transfer
transporters by loading
Nanoparticles/me Injected by Rabbit, nanoparticles (NPs) with
Lung
senchymal stem loading on NPs mice, and anticancer medicine. [56]
melanoma
cell (MSC) inside the body monkey MSC demonstrated a
greater medicine
ingestion ability than
fibroblasts
Cardiovascular diseases include myocardial infraction (MI) [58], ischemic impairment, coronary
artery disease (CAD), heart arrhythmias, pericardial disease, cardiomyopathy (heart muscle
disease), and congenital heart disease .All these illnesses are the basic main cause of mortality
and morbidity in the world . Modern therapeutic approaches have been developed to stop the
incidence of heart failure after myocardial infarction .Liposomes, silica NPs, dendrimers, cerium
oxide NPs, micelles, TiO2 NPs, stents with nano-coatings, microbubbles, and polymer–drug
conjugates are used for drug delivery. Magnetic nanoparticles like magneto liposomes (MLs) are
made up of the union of liposomes and magnetic nanoparticles. Cationic liposomes, per
fluorocarbon nanoparticles, polyelectrolyte nanoparticles, and polymeric nanoparticles are the
modified forms of nanocarriers. Different forms of NPs; their experiment studies show its role in
treatment of heart diseases.[59]
Page 43
Table 5: Role Of Nanomedicine In Heart Diseases
Experimental
Nanocarriers Agents Results References
Model
Balloon injured
Polymeric
carotid and stented AG-1295 and Inhibition of
(PLGA) [60]
porcine coronary AGL-2043 restenosis
nanoparticle
artery in rats
Human plasma a3b integrins,
In vitro
Perfluorocarbon lumps, surface-bound
fibrinolysis and in [61,62]
nanoparticles hyperlipidemic streptokinase,
vivo theranostics
animals others
Cationic Clinical test, Vascular Major [63]
nanoparticles patients with 60 to endothelial improvement in
99% stricture in growth factor is myocardial
main arteries, involved to perfusion
confined supply via encode viral
catheter (tube) vector
Page 44
[Drug Delivery Approach Of Nanotechnology] [Capter5]
Chapter V
Drug Delivery Approach Of Nanotechnology
Page 45
[Drug Delivery Approach of Nanotechnology][Chapter5]
5.1.Drug Delivery Approach in Skin Diseases

Diseases of the skin are cutaneous and follicular. certain days, nanotechnology is used to treat
certain dermatological conditions. With little side effects, nanoparticle administration is
recommended for the treatment of cutaneous diseases. Because of their poor penetration into skin
tissues, commonly used creams, gels, and ointments are inadequate for delivering medicines.
Polymeric, lipid, and surfactant nanocarriers are employed to address this. In order to cure skin
cancer, the polymeric micelles improve medication penetration into the skin tissue. Gold
nanoparticles, liposomes, and chitosan polymeric NPs can all be used to treat atopic dermatitis
by enhancing medication penetration into the dermal and epidermal layers, as demonstrated in
this work [64].Due to their minuscule size, gold nanoparticles have minimal toxicity and may
permeate the skin with ease. They are therefore often employed in nanocarrier formulation for
skin.
Fig 3: Mechanism Of Drug Delivery In Skin

[DrugDelivery Approach of Nanotechnology][Chapter5]
5.2. Drug Delivery Approach in Bone Diseases
Bone disorders comprise abnormalities in the bone caused by several pathological reasons,
including infections, fractures, trauma, osteoporosis, arthritis, and numerous other illnesses. The
proper mending of bones involves the fusion of biological components and nanomaterials in a
highly intricate process known as bone regeneration as a disease therapy. With the creation of
bone bioscaffolds, the combination of biomaterial and nanomaterial has decreased bone
implantation.
5.3. Mechanism of Drug Delivery In Bone Diseases
The drugs encapsulated inside the nanoparticle is delivered through blood to the targeted area in
the bones. The management of the sending nanoparticles as shown herenin .
Fig4 : Mechanism of nanomedicine delivery in bone diseases.
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[Drug Delivery Approach of Nanotechnology][Chapter5]
5.4 Drug Delivery Approach in Blood Diseases
There are various types of blood diseases, like hemopoietic blood disorder, as well as iron
deficiency, leukemia, anemia, hemophilia, platelet diseases, and blood cancer. The
conventionally used chemotherapeutic system causes damage to the immune system, with high
risk of mortality. Bone marrow transplant is also an expensive and intricate process. For
example, thalassemia is treated with deferoxamine, a chelating agent to treat excessive iron in the
blood. The siRNA-coated nanocomposite has the inhibitory activity for tumor cells in vivo .The
treatment of blood disorders with nanomedicine is still under investigation.
Fig 5: Mechanism of Drug Delivery In Blood Diseases
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[Application Of Nanotechnology In Medical Field] [Chapter7]
Chapter VI
Applications of Nanotechnology in the Medical Field
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6.1 Applications of Nanotechnology in Pharmaceutical Sciences
A brief overview of nanotechnological applications in pharmaceutical sciences has been covered

in the following section with a diagrammatic representation in Figure 4.
Fig6 : Applications Of Nanotechnology In Pharmaceutical
6.1.1. Nanoscience and Drug Dose Specifications
Because nanoscience makes it possible to produce better therapeutic medications with increased
efficacy and decreased toxicity, the pharmaceutical sector has undergone a revolution. Drug
pharmacokinetics can be enhanced by nanoparticles by enhancing the solubility, stability, and
bioavailability of the medicines [65]. Additionally, they may target certain tissues and cells,
which lessens adverse effects and increases their effectiveness.The exact criteria for medication
dosage and delivery are necessary due to the nanoscale size and distinct physicochemical
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features of nanoparticles. The size, shape, surface characteristics, and mode of administration of
nanoparticles all affect their dosage.For example, due to variations in absorption and
biodistribution, oral treatment may need a greater dosage to produce the same effect as
intravenous delivery [66].
6.1.2.Nanotechnology and Drug Delivery Technologies
Medication distribution has undergone a revolutionary change because to nanotechnology, which

offers more efficient and tailored medication administration while reducing adverse effects and
boosting therapeutic efficacy. Utilising nanoparticles that are engineered to transport medications
to the intended site of action is one way that nanotechnology is being applied to the delivery of
pharmaceuticals [67]. There are several benefits of using nanotechnology for medication
delivery. First, it makes it possible to deliver medications to particular parts of the body, such
tumours, inflammatory tissues, and contaminated regions, in a focused and regulated manner.
This minimises negative effects and lowers the quantity of medication needed. Second,
medications may be stabilised and made more soluble by using nanoparticles, which increases
the treatments' efficacy in treating illnesses.Thirdly, nanotechnology can increase the
bioavailability of drugs by enhancing their absorption and distribution in the body. This allows
for lower doses of drugs to be used, resulting in reduced toxicity [68]. In conclusion, the
application of nanotechnology in drug delivery has revolutionized the field of medicine. It has
provided an effective and targeted delivery of drugs, minimized side effects, and increased the
therapeutic efficacy of drugs. The future of drug delivery lies in the continued development of
nanotechnology-based drug delivery systems.
6.1.3. DNA Nanotechnology and Drug Delivery System
In the last several years, DNA pistols and DNA vaccinations have been launched as DNA-based
medication delivery technologies. An growing discipline of DNA nanotechnology is being
introduced in the nanomedicine business, based on similar concepts.Through the use of these
medical instruments, nanostructures and molecules can self-assemble, improving therapeutic
targeting and lowering the toxicity of the pharmaceuticals themselves. With the use of such
technology, toxicity measurements in conditions like cancer, where the primary concern is drug
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toxicity related to chemotherapeutic medications, may be handled with simplicity.DNA-based

nanostructures have been effectively combined with effective medication biomolecules, such
doxorubicin and CpG oligonucleotides, to boost cellular intake efficiency.In the future, RNA-
based drugs could be developed utilising concepts related to those used in DNA-based
medication [68].
Nanobiotechnology and gene therapy are two fields that often intersect in the development of
innovative therapeutic approaches for the treatment of various diseases. In gene therapy, DNA
molecules are introduced into the patient’s cells to replace defective or missing genes, with the
aim of treating genetic disorders and other diseases. One application of nanobiotechnology in
gene therapy is the use of nanoparticle-based delivery systems to transport therapeutic genes to
target cells [69]These nanocarriers protect the DNA molecules from degradation and enhance
their ability to penetrate the cell membrane, increasing the efficacy and safety of gene therapy .
The development of gene editing technologies, which employ nanoscale tools to precisely
change DNA sequences and fix genetic mutations, is another technique in nanobiotechnology
that supports gene therapy.Furthermore, real-time monitoring of gene expression and other
molecular activities using nanoparticle-based sensors might yield important data for personalised
therapy.Healthcare professionals currently employ cutting-edge treatment ideas like gene therapy
and molecular DNA-based remedies, and the introduction of nanotechnology has sped up these
developments [70]. Since the molecular level of genetic alteration and illness prevention forms
the basis of efficient gene therapy, nanoscale technology is critical to the field. Through
alterations, various kinds of organic and inorganic particles—both biodegradable and non-
biodegradable—made using nano-assemblies are being linked to gene therapy processes. These
structural combinations allow access to and binding of DNA across cellular surfaces [71].
Moreover, mixes of polymer-based nanoparticles are produced for injections of intravenous
medicine. The development of nanogenetic therapies has new opportunities because to these
upgraded technology. All things considered, it is expected that the marriage of
nanobiotechnology with gene therapy will produce better treatments for a range of ailments,
including infectious diseases, cancer, and genetic abnormalities.
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6.1.4. Green Nanotechnology-Driven Drug Delivery Assemblies
The majority of the processes used to create nanomedicines involve the physical and chemical
degradation of particles to the micro- and nanoscale. However, Concerns about adverse health
effects and environmental consequences have led to the application of green chemistry and green
engineering principles to the development of nanobiomedicine in nanomedicine. Producing
ecologically benign nanoassemblies with less harmful impacts on the environment and human
health is the aim of this green technology. The integration of green nanoassemblies with drugs,
vaccines, or diagnostic markers will be the next development in the field of green nanomedicine.
Numerous inorganic nanoassemblies that have been put on the market have been produced using
green engineering and nanotechnology [72]. Quantum dots, organic polymeric nanoparticles,
mesoporous silica nanoparticles, dendrimers, nanostructured lipid carriers, solid lipid
nanoparticles, and gold and silver nanoparticles are a few possible examples.
6.1.5. Nanotechnology—Antiviral and Antibacterial Applications
The causative agents of viral, bacterial, and other microscopic diseases work at the microscopic
level; therefore, the best way to fight against them is at the nanoscale. Nanotechnology is thus
the gateway to the cure and diagnosis of a wide range of viral, bacterial, and fungal diseases .
Although , Since ancient Greek medicine has long used metals like silver to treat illnesses, an
improved form of nanoscale-based material conversion has been demonstrated to increase the
effectiveness of both conventional and contemporary treatment approaches. A study conducted
by Nycryst Pharmaceuticals (Canada) revealed that nanosized silver particles exhibit greater
reactivity in the treatment of burns and wounds due to their tiny size and ease of skin penetration
[73]. With the aid of nanotechnology, researchers are now able to create powerful diagnostic
tools that leverage the power of genetic elucidation of irregularities at the gene level. The fields
of genomics and proteomics are already making significant contributions to the elucidation of
molecular insights into disease.According to research, there will soon be targeted and
personalised therapy options for preventative and regenerative medicine against pathogenic and
pathophysiological disorders that are based on nanotechnology [74]. These advantages are
combined with the new technology's ability to save money and time.
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6.2. Applications of Nanotechnology in Regenerative Medical Sciences
The study of generating and modifying materials at the molecular and atomic levels is known as
nanotechnology. Using substances that encourage bone development, bone regeneration
technology either regenerates new bone tissue or aids in the healing of already-existing bone
tissue.More and more, bone regeneration technology is utilising nanotechnology to develop more
effective, focused, and targeted bone-growth-promoting materials. To increase the efficacy of
therapy, researchers are looking at the use of nanoparticles to transport medications or other
chemicals that encourage bone development directly to the affected regions. Additionally,
scaffolds that resemble bone can be made using nanoparticles to assist direct the formation of
new bone and promote bone regeneration. Furthermore, extremely accurate and personalised
implants for bone regeneration may be made with the use of developments in 3D printing
technology that employ nanoscale materials.When relating nanotechnology to medicine, bone
weakening and dysfunction are common issues that nanotechnologists have identified as being
critically important. With the use of nanotechnology, some research is being done on the creation
and structure of bones.
6.2.1. Nanotechnology and Regenerative Medicine
Regenerative medicine is an interdisciplinary discipline of medicine that combines the

advantages of tissue engineering and cell therapy to create well-designed devices that cure,
maintain, enhance, and repair damaged and dead cells, tissues, and organs.It was previously
challenging to work with the body at the cellular level, but the development of nanoscale
technology has opened up a world of opportunity in regenerative medicine by allowing for the
manipulation of cells and their constituent parts to regulate the interconnected cellular responses
and extracellular material production.Thanks to the strong tissue regeneration properties of
nanoassemblies, tissue restoration has significantly improved. These technologies are being
directed for cellular adhesion, migration, differentiation, and other mechanical aspects that
initiate tissue regeneration .
Exploration in the field of nanomedicine is going on to manufacture nanoscale materials, such as

gold and silver nanoparticles, dendrimers, nanorods, carbon buckyballs, nanoshells, nanocubes,
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and many other forms of nanoparticles [74]. Each is specific to its linked properties, which can
be directly utilized in targeted tissues and organs. Multiple research groups are working
worldwide to explore the diagnostic, therapeutic, anti-viral, antifungal, and most importantly
anticancerous properties of these nano-agents .
6.3. Applications of Nanotechnology in Surgery
A brief overview of nanotechnological applications in surgery is covered in the following section

with a diagrammatic representation in Figure 5.
Fig7 :Application of nanotechnology in surgery
6.3.1. Nanotechnology and Anesthesia Induction
Anesthesia induction is a critical step in dental surgeries and other sensitive medical procedures,
such as brain surgeries. For such anesthesia induction procedures, researchers are working on
nanorobotic suspension mixtures that make a colloidal suspension with millions of nanoscale
active analgesic nanoparticles . These nanoparticles penetrate deeply to the level of loose tissue,
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working on the gingival and other sensitive areas of patients. The combinational principles of
chemical and temperature gradients and positional navigation, which are monitored and managed
by on-site nanocomputers, are used to carry out this transit of nanomaterials. The intended
impact is achieved more rapidly and evenly across the projected organ, such as the tooth surface,
thanks to this nanoscale anaesthetic activity. Additionally, the sensitivity action can be adjusted
for a specific tooth that needs surgery. To return tooth sensitivity to normal after surgery,
nanocomputers are used to drive nanorobots.
6.3.2. Surgical Nanorobotics and Nano-Bioelectric Medicine
The creation and application of small robots, or nanorobots, that are highly efficient and precise
surgical operators is known as surgical nanorobotics. Through the use of cutting-edge imaging
techniques, these nanorobots may be directed to precise places within the body where they can
carry out activities like medication delivery, tumour removal, or tissue restoration. On the other
hand, electrical impulses are used in nano-bioelectric medicine to promote the body's healing
mechanisms.In order to cure a variety of illnesses, such as chronic pain, wound healing, and
heart disease, this developing discipline focuses on using nanoscale technology to access and
regulate the electrical activity of cells and tissues.Nanobioelectric medicine and surgical
nanorobotics both have the power to transform medicine and improve patient medicine.However,
there is still much research needed to fully explore the potential of these technologies and ensure
their safety and efficacy
6.3.3. Implantable Medical Nanogenerators
As the name suggests, implanted, self-powered medical nanosensors are known as

nanogenerators. Their operation is based on the idea that mechanical energy from movement of
the body may be converted into an electric spark.The body uses glucose to produce chemical
energy, which is then converted by muscle into mechanical energy. These nanogenerators then
use this mechanical energy to produce electric energy, which is then used to charge and operate
implantable nanodevices, which are being produced for medical applications at a rapid pace
these days.Implantable medical nanogenerators (IMNGs) are small devices that produce
electrical energy using mechanical energy derived from body motions [75]. They can be inserted
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into the body to power a range of medical devices, such as medication delivery systems,
pacemakers, and neurostimulators.
6.4. Applications of Nanotechnology in Oncology Field
6.4.1. Nanotechnology and Cancer Treatment Strategies
In the field of medicine, efforts are always directed towards finding therapy and early detection
alternatives for complicated and incurable diseases like cancer.Researchers have a great chance
to create novel tools with nanotechnology, such as fluorescent materials, molecular diagnostic
kits, and tailored medications that might improve illness diagnosis and treatment in the future.To
improve therapeutic specificity, scientists are experimenting with several techniques to combine
already-available medicines with nanoparticles.
Fig8 :Nanotechnology And Cancer Treatment Strategies
Hundreds of particular anti-cancer chemicals that may be directed to tumour areas are carried by
nanomedicine. Furthermore, while delving further into the connections between nanomedicine
and cancer, it's important to keep in mind the tumour imaging and immunotherapy techniques
associated with this field.Scientists are moving away from traditional cancer therapy techniques
and towards targeted therapies that may be used either alone or in combination with already
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known anti-cancer medications due to the efficacy of nanomaterials in cancer therapy

[75].Enhancing the tumor-targeting efficacy of chemotherapeutic medications and optimising
their pharmacokinetic and pharmacodynamic characteristics are also important ways to decrease
their side effects. Nanorobotics is also being used in conjunction with gene therapy procedures to
treat cancer cells by heat-induced ablation.Nanotechnology in Cancer Diagnosis
The most obvious issue with cancer patients is the diagnosis. Because cancer is often discovered
too late, in the third or fourth stages, it is mostly incurable. Nanotechnology is being used to
combat this issue by enabling the early diagnosis of organ tumours.The use of nanotechnology in
in vivo bioimaging techniques in extracellular contexts offers a very sensitive and specific
multiplexed measurement capability for cancer biomarker detection. The topic of cancer
diagnostics has great promise for the application of nanotechnology. Because of their extreme
tiny size, nanoparticles are able to pass through blood-brain barriers and cell membranes. They
are therefore perfect for supplying medications and other therapeutic substances to cancerous
cells. They can also be used to find the disease's location and kind, as well as to detect cancer
cells.
6.4.2. Multifunctional, Multimodal, Theranostics-Based Anticancer Therapy
Multifunctional theranostics therapy is an emerging field in cancer treatment that combines

multiple modalities into a single treatment approach. This approach aims to both diagnose and
treat cancer using nanomaterials. Nanomaterials, such as nanoparticles, are highly versatile due
to their unique properties at the nanoscale [76]They can be engineered to have various
functionalities, such as imaging capabilities, drug delivery systems, and targeted therapy agents.
By using these multifunctional nanomaterials, theranostics therapy can provide simultaneous
cancer diagnosis and treatment . In parallel, the term multimodal refers to the combination of
multiple treatment modalities in a single therapy.
6.4.3. Targeted Nano Drug Delivery Technology for Cancer Therapy
Targeted nano drug delivery technology for cancer therapy is a form of treatment that uses nano-
sized particles to deliver drugs specifically to cancer cells in the body. By specifically binding to
cancer cells, these nanoparticles can minimise harm to healthy tissues and deliver medications
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directly to the tumour location.In cancer treatment, the creation of tailored nano drug delivery
systems offers a number of benefits. First off, by raising the concentration of the medications at
the locations of tumours, it can improve their efficacy. This enables the delivery of greater
dosages directly to cancer cells, which is especially significant for medicines with high toxicity
or limited solubility. Different kinds of targeted nano drug delivery systems, such as carbon
nanotubes, liposomes, polymeric nanoparticles, and dendrimers, are being investigated. By
attaching ligands or antibodies to certain receptors or proteins that are overexpressed on the
surface of cancer cells, these nanoparticles can be functionalized.
6.4.4. Nanotech Based Magnetic Drug Delivery Technology and Cancer Therapy
Nanotechnology and magnetic drug delivery technology are both innovative approaches in the
field of medicine that improve drug delivery and enhance treatment effectivenessUsing an
external magnetic field, magnetic drug delivery technology directs drug-loaded nanoparticles to a
particular location inside the body [77].It is possible to functionalize magnetic nanoparticles with
medications before administering them intravenously. The nanoparticles may be steered towards
a tumour or other desirable place by externally creating a magnetic field.With this strategy,
adverse effects can be decreased and systemic exposure can be minimised by more accurate
medication administration. By preventing the drug payload from degrading, nanoparticles can
increase stability and extend the time that the medication is released. Thus, a number of medical
fields have showed promise for the application of nanotechnology and magnetic drug delivery
technologies [78]. For instance, magnetic nanoparticles can be utilised to deliver chemotherapy
medications straight to tumours during cancer treatment., increasing drug concentration at the
tumor site and reducing toxicity in healthy tissues. This approach can enhance treatment efficacy
while minimizing adverse effects.
6.5 Applications of Nanotechnology in Dentistry
Nanodentistry is a separate branch of nanomedicine that involves a broad range of applications

of nanotechnology ranging from detection to diagnosis, to cure treatment options and prognostic
details about tooth functions .A wide spectrum of oral health-related issues can be dealt with
using nanomaterials .These nanomaterials derive their roots from tissue engineering and
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biotechnologically manufactured dental nanorobotics [79.]. Some recent advances under oral
nanotechnology may include treatment options such as anesthesia, dentition renaturalization,
hypersensitivity cures, orthodontic realignment problems, and modernized enameling options for
the maintenance of oral health
Fig 9 :Application Of Nanotechnology In Dentistry
6.5.1. Nanotechnologies, Tooth Repair, and Hypersensitivity Treatment
Researchers are still trying to use nanotechnology to the development of dental treatments and
cures. This might involve using nanomaterials to construct prosthetic teeth with sensitivity
controlled by nanorobotics or stimulating the body's natural biomineralization process.Using
nanoscale fabrication of nanorods produced from calcium hydroxyapatite crystals to assist
control tooth function, they are attempting to build the toughest tissue enamel. Reconstructive
dental nanoparticles are also used to provide patients with a quick and permanent remedy for
hypersensitivity.
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6.5.2. Tooth Repositioning and Renaturalization
Patients are more concerned with tooth repositioning because, in the event of a maladjustment, it
can lead to subsequent treatment or interruption of oral health. In this situation, orthodontic
nanorobots might be employed to manipulate tissues in order to achieve painlessly and smoothly
aligning, rotating, and repositioning the tooth [.Additionally, as time goes on, consumers' interest
in enhancing the aesthetic quality of their physical appearance has grown, giving rise to the
notion of dental aesthetics. In this sense, it is thought that nanotechnology can carry out
processes like extracting dental amalgams or remanufacturing teeth in conjunction with crowns,
fillings, and other similar alterations.Nanotechnology and Dental Durability .
In routine dental practices, a lot more work is being done to ensure tooth look and dental
longevity. In the form of nanostructured dental materials containing carbon nanotubes that offer
fracture-resistant qualities, nanotechnology offers a more durable and secure option.Furthermore,
more basic dentifrobots are being added to toothpastes and mouthwashes to continuously debride
calculus and clean teeth by replenishing dental surfaces.These dentifrobots can identify and
eliminate particular harmful bacteria from the mouth while maintaining a balanced population of
beneficial oral microflora.
6.6. Nanomedicine and COVID-19
During the COVID-19 pandemic, nanomedicine has played a crucial role in developing
diagnostic tools, treatment strategies, and vaccine delivery methods. The link between the
coronavirus and nanoparticles based on size and function is relatively straightforward. In terms
of size, both the virus particles and nanoparticles are tiny particles with a size on the nanoscale
[80]. This small size allows them to interact with each other on a very tiny scale. Similarly, in
terms of functional similarities, nanoparticles can be engineered or designed to have specific
functions. For example, some nanoparticles can be coated with molecules that make them stick
to viruses such as the coronavirus .This function is essential because it allows nanoparticles to
―grab onto‖ the virus. Thus, in the context of the coronavirus, scientists have explored how
nanoparticles can be used in various ways including detection, treatment, and protective
responses. Nanoparticles can be designed to bind to specific parts of the coronavirus.
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6.7. Nanoparticle Application In Non Parenteral Applications
6.7.1. Oral administration

For many reasons, oral drug delivery continues to be the preferred route of drug administration. It
is the oldest and the commonest mode of drug administration as it is safer, more convenient, does
not need assistance, non-invasive, often painless, the medicament need not be sterile and so is
cheaper .However, the oral route is not suitable for drugs that are poorly permeable or easily
degradable in the gastrointestinal tracts (GIT). For instance, delivery of proteins and peptides via
the oral route will be greatly impacted by barriers such as (i) epithelial cell lining; (ii) the mucus
layer; (iii) proteolytic enzymes in the gut lumen (such as pepsin, trypsin and chymotrypsin); and
(iv) proteolytic enzymes (endopeptidases), at the brush border membrane. Drug loaded in
nanoparticles will be protected from the enzymatic degradation along the GIT providing the
potential benefit of enhanced absorption. It has been reported that, particulate absorption takes
place mainly at the intestinal lymphatic tissues (the Peyer’s patches). The epithelial cell layer
overlying the Peyer’s patches contains Mcells. The differences between absorptive enterocytes and
M cells are expressed in that M cells have (a) underdeveloped microvillous and glycocalyx
structures, (b) apical microfolds, (c) increased intracellular vacuolization and (d) absence of mucus.
The follicle-associated epithelia (FAE) are made up of the M cells and absorptive enterocytes .It has
been reported that, the FAE and Mcells are predominantly responsible for particle uptake along the
GIT. In this regard, nanotechnology is reportedly gaining attention in the development of proteins,
peptides and DNA delivery systems [81].
6.7.2 Pulmonary administration
Medicine micronization is a major factor in today's improved medicine dosage form and
therapeutic efficacy. A medication can be administered directly to the lung by mechanical
capillary bed interception in the lungs if it is micronized into microspheres with the right particle
size. Drugs that are produced as 7–25 µm microspheres can be administered intravenously (IV)
to concentrate the microspheres in the lungs.By using this strategy, the concentration of the
pulmonary medicine may be increased, maximising its efficacy against certain pulmonary
illnesses like mycoplasmal pneumonia and reducing any negative side effects. The finished
nanoparticulate formulation can be inhaled as dry powder or as a nebulizer (metered dosage
inhalers). For several therapeutic situations, local medication administration to the lung is ideal.
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medicine micronization is a major factor in today's improved medicine dosage form and
therapeutic efficacy. A medication can be administered directly to the lung by mechanical
capillary bed interception in the lungs if it is micronized into microspheres with the right particle
size. Drugs that are produced as 7–25 µm microspheres can be administered intravenously (IV)
to concentrate the microspheres in the lungs.By using this strategy, the concentration of the
pulmonary medicine may be increased, maximising its efficacy against certain pulmonary
illnesses like mycoplasmal pneumonia and reducing any negative side effects. Conditions
include asthma, lung cancer, cystic fibrosis, and chronic pulmonary infections may be treated
with the final nanoparticulate formulation.. For both local and/or systemic delivery, the
effectiveness of drug delivery by inhalation may be greatly imparted by mucociliary clearance
[82].Studies have shown that nanoparticles may facilitate transport of drugs to the epithelium
while avoiding undesirable mucociliary clearance. Other benefits of nanoparticle-based
formulations are in the suitability for (i) sustained drug effect due to possible prolonged
residence of drug at the site of action or absorption; (ii) controlled or targeted drug delivery. The
small size of nanoparticles makes them highly suitable for pulmonary delivery because they can
easily be air borne and delivered to the alveolus. It is important that the components of the
nanoparticle formulation are biodegradable to avoid accumulation in the lungs and that they do
not cause irritation of the air ways and lung tissue. The control of the particle size of the
formulation during manufacture and the entire shelf life of the drug product is also very
important for an acceptable product [83].
6.7.3 .Topical administration
As noted by Majuru and Oyewumi the feasibility of applying nanoparticles in topical/cosmetic

preparations has been a subject of several commentaries. In any case, this dosage form utilizes
the advantages of nanoparticles such as (a) protection of labile compounds; (b) controlled release
of incorporated drugs; (c) ability of solid lipid nanoparticles to act as occlusive to increase the
water content of the skin; and (d) ability of nanoparticles to serve as physical barriers on the skin
for blocking UV light and, as such, for use in sunscreen formulations.
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[Toxicity And Safety Analysis Of Nanotechnology] [Chapter7]
Chapter VII
Toxicity And Safety Analysis Of Nanotechnology
Page 64
7.1 Toxicology and Safety Analyses of Nanotechnologies
The side effects of nanotechnology are of great concern for humans, animals, and the overall
environment. While the toxicity attached to these assemblies is poorly understood, the scientific
community remains unsure as to what level they can extend the applications of nanotechnology,
especially in medicine, which is quite a sensitive domain of healthcare .In previous years, some
nano-based products were introduced but later pulled back from the market owing to the reported
side effects in the general public. The risk assessment of nanomedicine is thus a critical topic and
needs to be assessed soon . Prioritising research on nanoparticle utilisation, dosage modification,
and safety is necessary. The wonders of nanotechnology itself may be used to environmental,
chemical, and biological remediation through the use of sensors and markers.Consumer product
toxicity profiling needs to be done precisely. In order to develop more modified, safe, and
effective nanoemulsions for use in the future, skin care and dental products containing various
nanomaterials, such as liposomes, cubosomes, solid lipid nanoparticles, and dendrimers, must be
carefully evaluated and their side effects identified [84].
Fig10 :Toxicity recorded by protein-based nanoparticles, lipid-based nanoparticles, and

metal nanoparticles.
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7.2 Metal-Based Nanoparticles
Superparamagnetic iron oxide (SPIONS) is one of the FDA-approved nanoparticles, used widely
in diagnostics as well as therapeutic application (hyperthermia, magnetic drug delivery,
treatment of anemia) .However, the recent years have observed expansion of SPIONs as
potential drug delivery systems to treat cancer and other diseases .But, Until their properties are
improved, the usage of SPIONS has been somewhat restricted because to worries about their
toxicity. Due to toxicity concerns and anaphylactic responses, certain SPIONS that were
previously authorised by the FDA for use in medical imaging have been withdrawn from usage.
Studies that have already been conducted have shown that there are problems with ROS, LDH
leakage, inflammation, DNA damage, and changes in mitochondrial function. Additionally,
SPIONs are known to affect the complement system, which might result in adverse effects linked
to innate immunity. FeridexTM is one such SPION-based medication that has been shown to
modify the complement system; the FDA has since withdrawn it.
Some of the recent studies have highlighted that the toxicity of SPIONs can be reduced by use
of coating agents. Polymers like polyethylene glycol (PEG), poly vinyl (PV), dextran, and
chitosan can enhance the half-life and stability of SPIONs and prevent aggregation within cells.
The study finds that when magnetic iron nanoparticles are coated with zwitter-ionic ligands, they
showed good stability and biodistribution and required levels of renal clearance. oxicity of
SPIONs is a critical issue which needs to be considered before its extensive use as a drug
delivery system. Though lots of research have been carried out to understand the toxicity
relation, it is crucial to dig deeper to enhance their property.
7.3. Lipid-Based Nanoparticles
In 2018, FDA EC approved another lipid RNAi-based drug named ONPATTRO by Alnylam
Pharmaceuticals for diseases caused due to altered TTR (Transthyretin) protein. Risk and safety
studies associated with the drug use indicate infusion-related reactions, which can be reduced
with vitamin A supplementation and premedication with certain drugs like antihistamines and
corticosteroids. Some of the common adverse reactions observed with use of drugs include
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respiratory symptoms, headache, and change in blood pressure. However, there are limited
studies to understand the use of this drug among pregnant women, patients with renal issues, etc
Due to their negative charge, certain PEG-liposomal formulations can cause anaphylactoid
responses, complement activation, hypersensitivity reactions (HSRs), and cardiac discomfort.
The effects of negatively charged PEGylated liposome nanocarriers were investigated by Hoven
et al. Different PEG liposomes were created, each with a different liposomal size, chain length,
surface concentration, and anchor molecule. Maximum complement activation was seen in PEG
anchored with cholesterol, whereas other modifications had minimal to modest effects.Szebeni et
al. carried out a similar investigation in which they assessed the doxil and hynic PEG liposomes
for complement activation and hypersensitivity.
7.4 Protein-Based Nanoparticles
Protein-based nanoparticles have received much attention in recent times due to their
biocompatibility, amphiphilicity, easy biodegradability, and reduced toxicity. Albumin, gelatin,
ferritin, fibroin, and casein are some of the widely used protein-based nanoparticles for drug
delivery .
Albumin-based nanocarriers (ANCs) are flexible proteins derived from human serum albumin
that are utilised to provide cancer therapies [85].With serum albumin nanoparticles, a significant
amount of medication can be incorporated into the particle matrix due to the different drug
binding sites present in the albumin molecule. HSA could be a useful analytical marker for those
suffering from autoimmune disorders. It has been stated that albumin NPs are very harmful to
healthy cells and unstable. The newly synthesised albumin NPs need to be stabilised or cross-
linked in order to get around this, extend their half-life in an aqueous environment, and/or
prevent the formation of protein macro-aggregates. Among the techniques that can be applied are
thermal treatment, high hydrodynamic pressure, and enzymatic cross-linking with
transglutaminase or genipin.
Albumin nanocarriers are used in the treatment of a variety of disorders in addition to cancer.
HSA-coupled TRAIL delivery, according to Byeon et al., could be a promising therapy for
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rheumatoid arthritis (RA), a chronic autoimmune disease marked by extreme synovial

hyperplasia and joint destruction. They also found that rats given CLT-encapsulated HSA
nanoparticles had milder hepatotoxicity, nephrotoxicity, and cardiotoxicity than rats given CLT
alone, according to serum analysis and histopathological examination.
Because of their cheap cost, biocompatibility, biodegradability, limited antigenicity, and

versatility in formulations, gelatin nanoparticles have lately been proposed as a viable choice for
parenteral formulations [86]. Gelatin is regarded by the US Food and Drug Administration as a
naturally occurring, biodegradable, and biocompatible material that may be used to provide
doxorubicin, cycloheximide, resveratrol, and other drugs for tumour treatment.
Toxicity and therapeutic efficacy such as the IC50, LD50, and EC50 of the casein can be
evaluated by standard pharmaceutical techniques. A 3-month dose-repeated toxicity test was
conducted to examine the safety of casein nanoparticles when administered orally to animals. It
was reported that the males and females treated with the maximum dose of 500 mg/Kg bw
developed comprehensive hyperchloremia after almost a month. A few cases of hypernatremia in
the females were also reported. It was concluded that the formation of drug aggregates with
casein nanoparticles results in highly localized concentrations at the sites of deposition that are
associated with local toxicity .This study indicates the side effects of protein-based nanoparticles,
casein, although further studies are required for the detailed analysis of casein nanoparticle’s
toxicity and adverse effects.
Several steps can be taken to guarantee the safe and sustainable use of nanomaterials in the
medical field. One such step is to conduct thorough and rigorous risk assessments, which should
be carried out to determine the possible risks and hazards associated with particular
nanomaterials prior to their deployment in medical applications. In a similar vein, sufficient
regulatory frameworks must exist to guarantee the secure handling, manufacture, and use of
nanomaterials [87].This covers the assessment of their safety, the specifications for labelling, and
the observation of their effects in medical environments.
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[Future Prospects Regarding Nano-Medical Applications] [Chapter8]
Chapter VIII
Future Prospects Regarding Nano-Medical

Applications
Page 69
8.1Future Prospects Regarding Nano-Medical Applications

Nanomaterials hold significant promise for various biomedical advancements and industrial
applications. However, their unique physicochemical properties raise concerns about their
potential impact on human health and the environment. In order for medical nanomaterials to
enter the market, there are many obstacles to overcome, such as FDA certifications and permits,
as well as safety and ethical concerns. In recent years, regulatory bodies worldwide have focused
on developing appropriate frameworks to ensure the safe and responsible use of nanomaterials.
Such an issue should be addressed more intensively in the coming years of nanotech research.
Review papers, in this regard, should aim to provide researchers, policymakers, and industry
professionals with a comprehensive understanding of the recent regulatory affairs surrounding
nanomaterials. By critically examining the current state of nanomaterial regulation, this paper
highlights the need for harmonization and collaboration among regulatory agencies worldwide.
Regulating industrialization affairs surrounding nanomaterials in medical sciences involves
several steps. It is important to note that these steps provide a general framework, but the specific
details and processes may vary depending on the jurisdiction and specific requirements of each
country or region.
8.1.1. Emerging nanomaterials
Newly developed nanomaterials including dendrimers, carbon nanotubes, polymers, block

copolymer micelles, and quantum dots are intended to improve medicine delivery and targeting.
Hexagonally bonded carbon atoms combine to form carbon nanotubes, which resemble hollow
tubes. They are being investigated for potential therapeutic uses, especially in the treatment of
cancer, as well as for the creation of novel diagnostic tools and nanosensors. One possible
application for carbon nanotubes is targeted medicine delivery.
The semiconductor nanocrystals known as quantum dots are made up of a metallic shell
enclosing an inorganic core. They can be applied as fluorescent labels for other drug carriers,
including liposomes, or as drug carriers themselves. They can support the development of
therapies that integrate molecular imaging for diagnostics with treatment, such as cancer. For
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both carbon nanotubes and quantum dots, toxicity is an important concern, and researchers are
looking at how to make these materials less toxic before using them for medical applications.
Dendrimers are molecules with a regular and highly branched tree-like structure. They measure
between 1 and 10 nanometres in diameter and have a hydrophobic internal cavity that can be
filled with hydrophobic molecules, for instance, anticancer drugs. Compared to other drug
carriers such as liposomes, dendrimers are mechanically more stable but can carry smaller
amounts of the drug.
8.1.2.Theranostics and personalised nanomedicine
Personalised medicine refers to a therapeutic approach tailored to the individual characteristics of

a patient through the use of techniques such as molecular profiling. In the future, nanotechnology
may allow us to receive individualised therapeutic treatments. Newly developed nanomedicines
include multi-component systems called theranostics that can, for example, incorporate both
therapeutic and diagnostic molecules. The resulting nano-system will allow diagnosis, drug
delivery and monitoring of the effects of the medicine. The development of such systems can
help to reach the goal of obtaining individualised therapies for several diseases.
The reason behind the increasing amount of research done in the direction of personalised
nanomedicine is that diseases such as cancer are extremely heterogeneous and the existing
treatments are effective only for certain patients and at a certain stage of the disease. The
administration of a theranostic agent to a patient can potentially allow monitoring of how well
the patient responds to the nanomedicine, as the imaging molecules enable the real-time
visualisation of the effect of the drug. As a result, drug dosage and treatment protocols can be
optimised and individualised during follow-up.
In the future, dentistry and periodontal therapy may become more sophisticated and efficient in
an attempt to control each patient's oral health at the microscopic level by preventing decay at the
source, which is bacteria. This is made possible in part by the development of nanotechnology.
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Building an extensive research centre is essential to fulfilling the stringent criteria for the
advancement of nanotechnologies.
Researchers are investigating how to carry out operations that are now completed by hand or
with equipment using tiny organisms. We call this idea "nanotechnology." Nanoassemblers are
tiny devices that can be programmed by a computer to carry out specific tasks. To fit into areas
that are difficult to access with the human hand or other forms of technology, the nanoassemblers
can have a smaller size than the nucleus of a cell. used to control these microscopic workers with
a computer to eliminate oral bacteria that leads to dental caries or even to fix areas on teeth
where decay has begun.
Nanotechnology has tremendous potential, but social issues of public acceptance, ethics,
regulation, and human safety must be addressed before molecular nanotechnology can be seen as
the possibility of providing high quality dental care to the 80% of the world's population that
currently receives no significant dental care.
Role of periodontitis will continue to evolve along the lines of currently visible trends. For
example, simple self-care neglect will become fewer, while cases involving cosmetic procedures,
acute trauma, or rare disease conditions will become relatively more commonplace.
Each patient's preferences and genetic makeup will be taken into account when making a
diagnosis and treatment plan. There will be an exciting increase in the number of treatment
possibilities. All of this will necessitate—even more so than in the present—the highest calibre
of technical proficiency and professional capabilities, which characterise modern periodontists
and dentists. Significant acceleration of developments is anticipated.
Drug delivery might be more accurately achieved with the use of nanometer and nanotube
technology. Technology ought to be able to target particular cells in a patient with cancer or
other serious illnesses. The use of toxic medications to treat certain diseases would become much
more focused, and as a result, less damaging to the body.
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[FDA approved and commercialized nanomedicines] [Chapter8]
Chapter IX
FDA approved and commercialized nanomedicines
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9.1.FDA approved and commercialized nanomedicines

9.1.1.Lipid-based nanoparticles
Approved marketed drug-loaded lipid-based nanoparticle
Drug Loaded Types Of Nanoparticles Trade Name Application
Daunorubicin Liposomal daunorubicin Daunoxome Karposi sarcoma
Cytarabine Liposomal cytarabine Depocyt Lymphoma
Vincristine Liposomal vincristine Marqibo Acute lymphocytic blood
Irinotecan Liposomal ironotecan Onivyde Pancreatic cancer
Amphotericin B Liposomal amphotericin B Ambisome Fungal infection
Verteporfin Liposomal verteporfin Visudyne Decreased vision
Doxorubicin Liposomal doxorubicin Doxil Ovarian cancer
The FDA authorised doxorubicin (Doxil), commonly referred to as Caelyx, in 1995. This
particular nanodrug is used to treat a variety of tumours, including AIDS-related Kaposi sarcoma
(KS) and metastatic ovarian cancer. "PEGylated liposomes" are unilamellar liposomes coated
with polyethylene glycol (PEG) that encapsulate a combination of doxorubicin (adriamycin).
These structures range in size from 80 to 90 nm. This DDS lengthens the half-life of circulation,
which improves drug bioavailability. An Indian pharmaceutical firm named Sun Pharma Global
FZE was the first to produce injectable Doxil; it received FDA clearance in 2013. Doxil works
by two different mechanisms: either it intercalates into the DNA molecule and destroys
topoisomerase and DNA repair, or it produces free radicals and reactive oxygen species inside
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the cell, which damages cell membranes and causes lipid peroxidation. To increase the EPR
impact of tumours, the second-generation PEGylated liposomal doxorubicin, also known as
Doxil or Lipobox, targets cells passively. Liposomal doxorubicin's capacity to lessen side
effects—drugs that can be harmful to various body organs, including the skin and heart—is
another of its key advantages.
9.1.2.(DaunoXome) daunorubicin
The FDA authorised liposomal daunorubicin, also marketed as DaunoXome, in 1996. Another
anthracycline medication called DaunoXome is used to treat HIV-associated Kaposi's sarcoma
(KS) and cancer. Furthermore, a number of clinical studies have shown that daunorubicin is
effective and appropriate for treating different kinds of leukaemia. DaunoXome has been
licenced as a first-line cytotoxic therapy in severe kidney disease (KS) due to its effectiveness
and fewer adverse effects when compared to other cytotoxic medications including vincristine,
bleomycin, and adriamycin. The liposomes are composed of lipid bilayers of cholesterol and
distearoyl phosphatidylcholine, with a molar ratio of 1:2. They have an estimated diameter of 45
nm. Lipid:daunorubicin has a weight ratio of 18.7:11 in DaunoXome. While the precise
mechanism underlying DaunoXome specificity remains unclear, it is thought to be the
consequence of enhanced permeability of tumor neovasculature (EPR effect).
9.1.3. Onivyde(Irinotecan)
In 2015, the FDA authorised Onivyldan, a derivative of irinotelatinoid nanoform (MM-398). It

has also been demonstrated that liposomal irinotecan and other anticancer medications work in
concert. Patients with advanced pancreatic cancer who had irinosuccinate, 5-fluoracylinic acid,
folinic acid, and oxalate folinamide therapy had better results. Due to tumour overexpression,
nanoliposomal formulations have a longer half-life, passive tumour targeting, and fewer adverse
effects. Onivyde still causes certain adverse effects, nevertheless, such as baldness, vomiting,
diarrhoea, and stomach discomfort.
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9.1.4.Cytarabine (DepoCyt)
In 1999, DepoCyt was approved under the fast approval process. It is a liposomal version of
cytarabine made with Depofoam technology. It was given FDA approval in 2007 to treat
lymphomatic meningitis, a potentially fatal illness. Liposomal medication was solely injected
intrathecally into the spine in this instance. Triolein, dipalmitoyl phosphatidylglycerol,
phosphatidylcholine, and cholesterol are the ingredients of the liposomal formulation. The half-
life of this unique liposomal formulation is forty times greater than that of regular cytarabine. A
sustained-release version called DepoCyt is meant to be injected right away into the
cerebrospinal fluid. This anticancer medication can interfere with DNA polymerase and impact
cells during S-phase cell cycle.
9.1.5.Marqibo (vincristine)
The FDA authorised liposomal vincristine sulphate, often referred to as Marqibo, in 2012.
Vincristine is an anticancer drug that is an alkaloid that binds to tubulin and prevents cell
division. Vincristine is included in sphingomyelin/cholesterol liposomes as Marqibo. Marqibo
(2.25 mg/m2) was given to adult patients with Philadelphia chromosome-negative chronic
myelogenous leukaemia, and 35% of the patients experienced a favourable response. By
contrast, the area under the plasma drug concentration vs time graph indicates a slower clearance
rate for traditional vincristine. Other advantages of liposomal vincristine include a longer half-
life in circulation and little systemic toxicity. Constipation, nausea, weakness, diarrhoea, and
sleeplessness are significant side effects.
9.1.6-.Amphotericin B (AmBisome)
AmBisome, the liposomal form of amphotericin B (AmB) or L-AmB, is an antifungal agent

administered to treat a broad spectrum of fungal pathogens. Because it does not work through
enzyme inhibition, AmB does not lead to the emergence of resistant fungal species, like other
antifungal agents do. Fungizone and standard injectable water-soluble AmB have been
developed in an attempt to find new formulations that alleviate toxicity. Studies have been
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carried out on murine models concentrating on particle size, AmB content, physicochemical
stability, and toxicity. The benefits of liposomal AmBisome include improved pharmacokinetic
properties and circulation stability, decreased accumulation in normal uninfected tissue, and
decreased mammalian cell toxicity compared to fungal cells, making it far safer than Fungizone.
AmBisome allows the drug to cross the liposome membrane and then bind to ergosterol in the
fungal membrane, resulting in ion leakage and, ultimately, fungal cell death
9.2.Polymer-based nanoparticles
Table 6 :Approved marketed drug-loaded polymer-based nanoparticle
Drug Loaded Types of nanoparticles Trade name Application
Certolizumab pegol PEGylated antibody fragment Cimzia Chron’s diseases
Glatiramer acetate Random copolymer of L- Copaxone Multiple sclerosis

glutamate
Leuprolide acetate Leuprolide acetate and Eligard Prostate cancer
polymer
Pegfilgrastim PEGylated GCSF protein Neulasta Leukopenia by
Chemotherapy
Peginterferon alfa 2A PEGylated IFN alfa 2A Pegasys Hepatitis B and C
protein
Peginterferon alfa 2B PEGylated IFN alfa Peglntron Hepatitis C
2ABprotein
Pegvisomat PEGylated HGH receptor Somavert Acromegaly
antagonist
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9.2.2.Pegol certolizumab (Cimzia)
The FDA authorised certolizumab pegol in 2008; it is a PEGylated inhibitor of tumour necrosis
factor-alpha (TNF-α). Cimzia is a PEGylated Fab fragment that binds to TNF-α selectively to
neutralise its action. It is a portion of a humanised IgG antibody that does not include the Fc
region. Cimzia is used to treat ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis.
All of these illnesses are associated with autoimmunity, which is the patient's abnormal immune
reaction to healthy cells. Since it appears that the contents of the gut lumen, rather than self-
antigens, cause the reaction, Crohn's disease is not technically classified as an autoimmune
disease. TNF-α is a pro-inflammatory cytokine that is pluripotent and may be a major factor in
the autoimmune onslaught.
9.2.3. Pegaspargase (Oncaspar)
The FDA authorised Oncaspar, also known as pegaspargase, in 1994. Oncaspar is a PEGylated-l-
asparaginase. This medication is used to treat both chronic myelogenous leukaemia and acute
lymphoblastic leukaemia. It can also be substituted in leukaemia patients who exhibit
hypersensitivity to l-asparaginase produced from Escherichia coli. The advantage of oncaspar is
that it only has to be taken every two weeks, whereas l-asparaginase, the native chemical, needs
to be taken three times a week. Oncaspar's extended half-life as a result of PEGylation is the only
reason it has to be administered less often. Oncaspar also shows a significant reduction in
hypersensitivity and overall cost savings for patients.
9.2.4. Pegvisomant (Somavert)
The FDA authorised Somavert (pegvisomant [B2036-PEG]) in 2003 as a PEGylated analogue of

human growth hormone (GH) for the treatment of acromegaly. In those with acromegaly, the
pituitary gland secretes excessive amounts of growth hormone, which causes abnormal
expansion of the hands, feet, forehead, and jaw. As a GH receptor antagonist, somavert reduces
blood levels of IGF-I, one of the key mediators of GH activity, by at least 50% by blocking GH
binding and interfering with GH signal transduction pathways. As predicted, PEGylation of
Somavert's active component (B2036) causes an extended half-life and decreased clearance
(estimated to be 28 mL/h for subcutaneous injection of 10–20 mg).
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9.2.5.Methoxy PEG glycol-epoetin β (Mircera)
Mircera or epoetin β (EPO) conjugated to methoxy-PEG is a drug formulation used to treat

anemia. Both the European Commission and the FDA-approved Mircera in 2007. EPO is a
genetically recombinant form of erythropoietin capable of stimulating erythropoiesis by
functioning on the erythropoietin receptors of bone marrow progenitor cells. To create Mircera,
the PEG moiety (∼60 kD) is first linked with butanoic acid, and the NHS-modified structure is
connected to the lysine moiety of the EPO structure via amide bonds. This formulation provides
a controlled release system with a half-life of ∼135 h. Naked EPO has a half-life of 7–20 h. The
main benefit is the less frequent administration of Mircera. The administration of Mircera usually
entails intravenous or subcutaneous injection of 0.6 μg/kg every 2 weeks.
9.2.6. Peginterferon alfa-2b (PEG-INTRON)
PEG interferon alfa-2b is a long-acting interferon; its structure contains an alpha interferon (INF)
molecule conjugated to a mono PEG chain through succinimidyl carbonate. Compared to the
regular interferon molecule, its longer half-life and slower elimination lead to less frequent
administration. PEG interferon alfa-2b was approved by the FDA in 2001 and is commonly used
as a monotherapy or in combination with other medicines, such as ribavirin, to treat chronic
hepatitis C.
Table 7:Approved marketed drug-loaded crystalline nanoparticles
Drug Loaded Types of nanoparticles Trade name Application
Aprepitant Nanocrystal Emend Vomiting agent
Fenofibrate Nanocrystal Tricor Hyperlipidemia
Sirolimus Nanocrystal Rapamune Immunosuppressant
Megestrol acetate
Nanocrystal MegaceES Anorexia
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Dexmethylphenidate Nanocrystal Focalin XR Mental stimulant

HCl
Metyhlphenidate
Nanocrystal Ritalin LA Mental stimulant
HCl
Tizanidine HCl Nanocrystal Zanaflex Mucle relaxant
9.2.6. Aprepitant (Emend)
Approved by the FDA in 2003, Emend is the nanocrystalline version of the antiemetic
medication aprepitant. It is used, particularly in courses with high-dose cis-platin, to avoid
nausea and vomiting during chemotherapy. Given its strong emetogenicity, cis-platin is known to
cause nausea and vomiting in patients. A human substance-P-ligand antagonist, Aprepitant has a
strong affinity for neurokinin-1 (NK1) receptors in the postrema region of the brain, sometimes
referred to as the vomiting area of the brain. The advantage of aprepitant over other NK1
antagonists is that it has little to no selectivity for dopamine, corticosteroid, or serotonin (5-HT3)
receptors.
9.2.7. Sirolimus (Rapamune)
The FDA 80uthorized Rapamune, also known as sirolimus (rapamycin), as the first medication
of the nanocrystalline kind in 2000. It is employed to stop kidney transplant rejection.
Streptomyces hygroscopicus is the source of the macrocyclic triene antibiotic sirolimux, which
has immunosuppressive properties. Better bioavailability is made possible by the Elan Drug
Delivery Nanocrystals technology, which involves bead/pearl grinding and significantly
improves the release profile of poorly soluble medications. While Rapamune’s longer release is
not totally necessary, the nanoformulation makes oral administration possible and allows for
more easy storage.
9.2.8. Methylphenidate (Ritalin)
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Ritalin, also known as methylphenidate, was approved by the FDA in 1955 to treat hyperactivity
disorders in children. The medication is primarily used to treat attention deficit hyperactivity
disorder (ADHD). Since the 1990s, the drug has been increasingly administered for more
prevalent ADHD diagnoses. In 2007, in England, general practitioners administered this drug to
around 420,000 individuals, and by 2012, the amount had increased to 657,000, reflecting a 56%
increase. According to research, in disorders such as ADHD, norepinephrine and dopamine
release are imbalanced, and the brain’s dopamine and norepinephrine receptor control is
dysregulated. Ritalin inhibits dopamine reuptake, thus increasing the concentration of dopamine
in the synaptic cleft
9.2.9. (Focalin XR) Dexmethylphenidate HCl
The extended-release version of dexmethylphenidate, called Focalin XR, has a bimodal release
profile. Focalin XR is manufactured using a unique SODAS (spheroidal oral drug absorption
system) technology. Half of the dosage is included in each focal XR bead-filled capsule as
immediate-release beads and the other half is present as entero-coated delayed-release beads.
This results in an instant release of dexmethylphenidate and a second delayed release of the drug.
The powder form of dexmethylphenidate hydrochloride is white to off-white in colour and has an
acidic solution. It dissolves readily in methanol and water, partially in acetone and chloroform,
and soluble in alcohol. For the treatment of ADHD, focused XR is advised in patients six years
of age and older.
9.2.10.Tizanidine HCl (Zanaflex)
Zanaflex (tizanidine hydrochloride) is a central alpha-2-adrenergic agonist. Tizanidine HCl is a

fine crystalline powder that is white to off-white and odorless, although it sometimes has a faint
characteristic odor. In water and methanol, tizanidine is slightly soluble, and its solubility in
water decreases as the pH increases. The molecular formula of izanidine is C9H8ClN5S–HCl,
with a molecular weight of 290.2. Zanaflex has been suggested for the treatment of spasticity.
Due to its limited duration of therapeutic benefit, Zanaflex therapy should be reserved for
particular everyday tasks and periods when relief of spasticity is necessary. Tizanidine is a key
agonist of the alpha-2-adrenergic receptor, which probably decreases spasticity by increasing
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motor neuron presynaptic inhibition. Tizanidine’s effects on polysynaptic pathways are strong.
The cumulative influence of these actions is assumed to decrease spinal motor neuron facilitation
9.3. Regulations Of Nanomaterials In Medical science
Table 8: Steps needed to regulate industrialization affairs surrounding nanomaterials in

the medical sciences.
Steps Needed for

Sr.
Industrial
No.
Regulation Brief Explanation Ref
There is need to conduct a comprehensive risk assessment to

understand the potential risks associated with the use of
1 Risk assessment: nanomaterials in medical applications. Evaluate the toxicity, [86]
exposure pathways, and potential environmental impacts of
these materials.
Develop a regulatory framework specifically tailored to govern

the industrialization of nanomaterials in medical sciences. This
Regulatory
2 framework should consider existing regulations and guidelines [87]
framework
but also address the unique properties and potential risks posed
by nanomaterials.
Establish criteria for classifying and characterizing different

types of nanomaterials used in medical sciences. This should
Classification and
3 include their physical and chemical properties, intended uses, [88]
characterization
and potential risks. This information will assist in determining
appropriate regulations and handling requirements
Product registration Introduce a registration or approval process for nanomaterials

4 and safety used in medical applications. Manufacturers must submit [89]
assessment detailed information about the materials, including their
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synthesis methods, intended applications, potential hazards,

and safety data. Conduct a thorough safety assessment base on
this information before granting approvals.
Labeling and Implement labeling requirements to ensure proper [89]

traceability identification and traceability of medical products that contain
5 nanomaterials. Labels should provide clear information about
the presence of nanomaterials, their type, concentration, and
any potential risks associated with their use.
Establish manufacturing standards and best practices

specifically for nanomaterials used in medical applications.
Manufacturing
6 These standards should address issues such as quality control, [90]
standards
handling, storage, transportation, and waste management,
considering the unique properties of nanomaterials.
Develop a surveillance system to monitor the usage,

performance, and safety of nanomaterials in medical sciences.
Monitoring and
7 Regularly review and update regulations based on emerging [91]
surveillance
scientific evidence, advancements in technology, and any new
risks identified.
Foster collaboration and information-sharing initiatives with

other regulatory bodies and international organizations to
Collaboration and
harmonize standards and regulations for nanomaterials used in
8 international [92.93]
medical sciences. This will help avoid duplication of efforts,
harmonization
facilitate global trade, and ensure a consistent level of safety
worldwide.
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[Conclusion ] [Chapter10]
Chapter X
Conclusion
Page 84
[Conclusion ] [Chapter10]
10. Conclusion
The future of nanotechnology in healthcare and medicine holds immense potential for
revolutionizing the way we diagnose, treat, and prevent diseases. Nanotechnology involves the
manipulation of materials at such a small scale where the properties of materials significantly
differ from their bulk counterparts, allowing for precise control of their physical, chemical, and
biological properties. This opens up new opportunities for developing novel therapies, targeted
drug delivery systems, and sensitive diagnostic tools. In addition to drug delivery, targeted
delivery, improved drugs, limited dosages, and reduced systematic side effects, nanoparticles can
also be used to enhance the efficacy of existing drugs by improving their solubility, stability, and
bioavailability. Additionally, nanotechnology-based sensors and devices can monitor patient
health in real-time, enabling early detection and personalized treatment plans. In the future,
nanotechnology may even enable the development of nanorobots that can navigate through the
bloodstream to target and destroy cancer cells or deliver payloads of drugs to particular tissues.
The broad spectrum of nanomedicine covered in this article may be lacking in various other
aspects of nanomedicine still in the research pipeline. The vision of nanotechnology might seem
heretic and abstract, similar to the in silico experimentation and computational bioinformatics
field that was criticized a few years back. However, the field of nanobiotechnology is rapidly
appearing as a cutting-edge technology of the 21st century, with diverse implications in science
and technology. The theoretical knowledge is there, and applied research is ongoing to make it
more progressive. It is predicted that soon, nanotechnology will not remain an option but rather
be compulsory in the medical industry. As soon as the cost associated with technology becomes
accessible, it is predicted to affect our dentistry, healthcare, and human life more profoundly than
in the past. The major need is to curtail the toxicological concerns and risks that are attached to
high doses and the excessive use of nanomaterials in drug and treatment regimes. This is
important if scientists want to enable the successful operation of nanotechnology in medicine.
Overall, the future of nanotechnology in healthcare and medicine holds great promise for
improving patient outcomes and revolutionizing the way we approach disease prevention and
treatment.
Page 85
[Referrences] [Chapter11]
Chapter XI
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A Review Article On Nanotechnology :Emerging Drug

Delivery System In Healthcare And Medicine

A Dissertation Submitted To The Department In Partial

A Mission With a Vision

I wish to profound gratitude to my project supervisor MD Shajalal Reza,Lecturer, Department

1.1 What Is Nanotechnolog ……………………………………………………… 7

1.5.1. Micelles …………………………………………………………………... 12

1.5.2 Liposomes ……………………………………………………………….. 12

1.5.3. Microemulsions …………………………………………………………. 13

1.5.4. Dendrimers ……………………………………………………………….. 13

1.5.5. Carbon Nanotubes ……………………………………………………….. 14

1.5.6. Metalic Nanoparticles …………………………………………………… 14

1.5.7. Quantum Dots ……………………………………………………………. 14

1.6. Some Natural Polymers In Nanodrug Delivery ……………………………. 15

1.6.1. Starch ……………………………………………………………………. 15

1.6.2. Chitosan ………………………………………………………………... 15

1.6.3. Gelatin …………………………………………………………………… 16

1.6.4. Hydroxyapatite-Based Nanoparticles ………………………………….. 16

Chapter 2. Literature Review Of Nanotechnology …………………………………… 17

Chapter 3 . Mechanism Of Nanotechnology Across BBB ……………………………. 27

3.1. Mechanism Of Nanotechnology Across BBB ……………………………... 27

3.2. Advantages And Disadvantages Of Nanotechnology ……………………… 28

Chapter 4. Role of Nanocarriers In Major Types Of Cancer ……………………….. 29

4.1. Brain Cancer ………………………………………………………………. 31

4.2. Breast Cancer ……………………………………………………………… 33

Chapter 5. Drug Deivery Approach ………………………………………………… 38

5.1. Drug Delivery Approach In Skin Diseases ……………………………… 41

5.2. Drug Delivery approach in bone diseases ……………………………….. 42

5.3 . Mechanism of Drug delivery In bone diseases …………………………... 42

5.4. Drug delivery approach in blood diseases ………………………………. 43

Chapter 6. Application Of Nanotechnology In Medical Field ………………………. 44

6.1. application of nanotechnology in pharma science ……………………….. 45

6.1.1. Nanoscience and dryg dose specification …………………………… 46

6.1.2. Nanotechnology and drug delivery ………………………………….. 46

6.1.3. DNA and drug delivery system ………………………………………. 47

6.1.4. Green nanotechnology ………………………………………………. 47

6.1.5. Antiviral and antibacterial application ……………………………... 47

6.2. Application In regenerative medical science ………………………………. 48

6.2.1. Nanotechnology and regenerative medicine ………………………... 49

6.3. Nanotechnology in surgery …………………………………………………. 50

6.3.1. Nanotechnology and Anesthesia induction …………………………. 50

6.3.2. Surgical nanorobotics and nanoelectric medicine …………………... 51

6.3.3. Implantable medical nanogenerators ………………………………... 51

6.4. Application Of Nanotechnology in oncology field ………………………….. 52

6.4.1. Nanotechnology and cancer treatment strategies …………………….. 52

6.4.2. Multifunctional, multimodal based anticancer therapy ……………… 53

6.4.3. Targeted Nanodrug delivery technique for cancer therapy…………… 53

6.4.4. Nanotechnology based dug delivery technique and cancer therapy…… 54

6.5. Application of nanotechnology in dentistry…………………………………. 54

6.5.2. Tooth repositioning and renaturalization ……………………………. 56

6.6. Nanomedicine and Covid 19 ………………………………………………… 56

6.7. Nanoparticle application in nonparenteral ………………………………… 57

6.7.1. Oral Administration …………………………………………………… 57

6.7.2. Pulmonary Administration……………………………………………… 57

6.7.3. Topical Administratio ………………………………………………….. 58

Chapter 7. Toxicity and safety analysys of nanotechnology …………………………... 59

7.1. Toxicity and safety analysys of nanotechnology ……………………………. 60

7.2 Metal based nanoparticle …………………………………………………….. 61

7.3 Lipid based nanoparticle ……………………………………………………... 61