Anticancer Drug Delivery

This study was performed to asses and establishes the prevalence of Polypharmacy in geriatric population in the Medicine ward of Rajah Muthaiya Medical College and Hospital, Annamalai University, during one year from January 2013 to January 2014. Demographic analyses of this prospective study revealed that out of 520 patients, 342 (65.76%) were males and 178 (34.23%) were females. All the collected prescriptions were scrutinized for Polypharmacy and were categorized as minor Polypharmacy -concurrent use of ≤ 5 drugs; and major Polypharmacy -concurrent use of > 5 drugs. Out of 502 Prescriptions 61(11.73%) prescriptions were minor Polypharmacy and 457(88.26%) prescriptions were major Polypharmacy. The maximum patients were in the age group of 60-64 (38.84%) range lead to a significant increase in the number of medications. The most common diseases associated systems were Cardiovascular system 147 (28.26 %) patients, and followed by Respiratory system 103(19.80%). Our results show that there is a higher prevalence of Polypharmacy among the males than females. The length of hospital stay of geriatric patients is increase in major Polypharmacy compare with minor Polypharmacy. The prevalence of cardiovascular drugs and respiratory drugs were often involved in Polypharmacy among geriatric patients. Polypharmacy is very common among geriatric patient and health care professional’s interventions to improve the optimal use of medication in geriatric could lead to reduction in the drug related problems associated with Polypharmacy.

Anti-inflammatory, anti-oxidant, anti-cancerous,  radioprotective and
anti-microbial properties of ginger (Zingiber officinale) rhizome are
well  recognized  worldwide.  Ginger  consumption  also  helps  in  the
management  of  inflammatory  damage  in  Alzheimer’s  and
Parkinson’s  disease.  Biological  properties  of  ginger  rhizome  are
attributed  to  its  active  compounds  including,  gingerols,  shogaols,
paradols  and  zingerone.  Zingerone  is  active  component  of  dried
ginger  rhizome  and  used  in  food  industry  as  flavouring  agent.
Various  observations  on  the  protective  role  of  zingerone  against
radiation  induced  oxidative  stress;  tissue  inflammatory  damage  and
drug  induced  toxicity  have  been  made  using  a  wide  range  of
experimental  models.  Mechanism  of  antioxidant  and  antiinflammatory  action  of  zingerone  has  been  linked  to potent  radical
scavenging  effect, causing  alteration in  gene/protein expression and
interference  with  intracellular  cell  signalling  pathways  of
inflammation.  Our  laboratory  for  the  first  time  revealed  antibiofilm
activity  of  zingerone  against  opportunistic  pathogen  Pseudomonas
aeruginosa. This study suggested that zingerone can be explored as a
safe  anti-infective  agent  against  P.  aeruginosa biofilm  associated
infections.  Hence,  comprehensive  information  showing  health
benefits of zingerone are urgently needed that may provide an update
on  its  therapeutic  potential.  We  conducted  a  detailed  search  of
literature  to  summarize  the  proven  health  benefits  and  biological
properties of zingerone. This review article summarizes in detail the
in vitroand in vivopharmacological benefits of zingerone.

Nanohydrogel combines the advantages of hydrogel and nano particulate systems. Similar to the hydrogel and macrogel, nanohydrogel can protect the drug and control drug release by stimuli responsive conformation or biodegradable bond into the polymer networks. Nanohydrogel has drawn huge interest due to their potential applications, such as carrier in target-specific controlled drug delivery, absorbents, chemical/biological sensors, and bio-mimetic materials. Similar to the nanoparticles, stimuli responsive nanohydrogel can easily be delivered in the liquid form for parenteral drug delivery application. This review highlights the methods to prepare nanohydrogel based on natural and synthetic polymers for diverse applications in drug delivery. It also encompasses the drug loading and drug release mechanism of the nanohydrogel formulation and patents related to the composition and chemical methods for preparation of nanohydrogel formulation with current status in clinical trials.

Chewing  gums  are  mobile  drug  delivery  systems.  Unlike  chewable
tablets medicated  gums are not supposed to be swallowed and may
be  removed  from  the  site  of  application  without  resort  to  invasive
means  and  medicated  chewing  gum  MCG  is  solid,  single  dose
preparation. As for as patient convenience is concerned it is discrete
and easy administration without water promotes higher compliance.
Since  it  can  be  taken  anywhere,  a  chewing  gum  formulation  is  an
excellent  choice  for  acute  medication.  The  advantages  for  children
and  for  patients  who  find  swallowing  tablets  difficult  are  obvious.
The medicated chewing gums are solid, single dose preparations with
a base consisting mainly of gums that are intended to be chewed, but
not  swallowed.  They  contain  one  or  more  active  substances,  which
are  released  by  chewing  and  are  intended  to  be  used for  local
treatment  of  mouth  diseases  or  systemic  delivery  after  absorption
through the buccal mucosa. This concept is supported by statements
that chewing sugar free gum can help reduce the risk of dental caries
(cavities).  The  objective  of  this  systematic  study  is  to  appraise
existing  evidence  concerning  a  possible  therapeutic effect  of  sugarfree  chewing  gum  for  patients.  MCG  represents  the  newest  system
with  potential  uses  in  pharmaceuticals,  over  the  counter  medicines
and nutraceuticals.

The main objective of this study was to assess awareness of danger
signs of pregnancy and its associated factors in Mekelle public
hospitals, 2014.
Institutional based cross sectional study was conducted among 422
pregnant mothers. Data was collected using interviewer administered
questionnaire; it was entered and analyzed using SPSS version 16.
The data were presented using texts, graphs and tables.
Out of the total participants of this study 79.6% mothers had
information about danger signs of pregnancy from which 61.9%
mothers had information about vaginal bleeding followed by sudden
gush of fluid before labor which was mentioned by 41.9% of
respondents. Severe unusual abdominal pain was the least known
danger signs as mentioned by 19 % of mothers. The main source of
information for the danger signs was health personnel and
Negligence was the main reason for not having good awareness about
danger signs of pregnancy.
Therefore, health extension workers should strengthen their
awareness creation activities; community mobilization and health
education should be considered with policy makers and other
interested organizations.

oligonucleotides have predominant role in its delivery for various
diseases. Objective: Antisense compounds are biological
molecules consisting of small ribonucleic acid (RNA) or
deoxyribonucleic acid (DNA) segments (Oligonucleotide) which
have enormous potential for the treatment of number of diseases.
Methods: All the methods analyzed were obtained through high
impact articles. Results: Several impediments were made to
Oligonucleotide for its widespread usage as them as drugs to
overcome their lack of stability in physiological fluids and their
poor penetration into cells. Experiments like, association with or
encapsulation within nano-and micro sized drug delivery systems,
lipids and polymers could help to increase the efficiency of
oligonucleotide delivery. This review discusses the use of cationic
lipids, Cell penetrating peptides, nanoparticles, microparticles and
several novel methods that have recently been explored as delivery
vehicles. Conclusion: The use of naked Oligonucleotide given a
clear cut way to new targets for potential therapeutic compounds.
Apart this, antisense therapy represents a promising and evolving
approach to the management of numerous diseases in which a
specific abnormality has been identified as a primary or major
contributing etiologic factor. In near future, authors strongly
believe that antisense therapy will give a positive way for number
of In vitro experiments and break through for many life
threatening diseases.

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

Febuxostat is a urate lowering drug, an inhibitor of xanthine
oxidase used in the treatment of hyperuricemia and chronic gout. The
drug shows dissolution-rate limited absorption, there by poor and
variable bioavailability. It needs enhancement in bioavailability to
derive maximum therapeutic efficacy. The main objective of the
present research work is to enhance the solubility and dissolution rate
of Febuxostat by preparing the Spherical agglomerates. Spherical
agglomerates were prepared by the quasi emulsion solvent diffusion
method. N, N-dimethyl form amide, chloroform and water were
selected as good solvent, bridging liquid and poor solvents
respectively. Polyethylene glycol, Poloxomer- F68 and Polyvinyl
alcohol were used as a carrier. Among all the formulations prepared,
spherical agglomerates prepared with Febuxostat and Poloxomer-
F68 in 1:1 ratio showed highest drug release in 60 minutes. Spherical
agglomerates prepared with Febuxostat and Poloxomer- F68 in 1:1
ratio was used in the preparation of orodispersible tablets. To study
the influence of superdisintegrants on performance of Febuxostat
Orodispersible Tablets, a set of three formulations (K1, K2, K3) were
prepared using three superdisintegrants sodium starch glycolate,
Croscarmalose sodium and Crospovidone . The orodispersible tablets
of Febuxostat prepared with Crospovidone showed rapid drug release
when compared to pure drug and other tablet formulations.

The present study was aimed to formulate and evaluate fast
dissolving oral films of Zolmitriptan using sodium alginate, xanthan
gum and sodium starch glycolate, guar gum. The suitable plasticizer
and its concentration were selected on the basis of flexibility, tensile
strength and stickiness of the film. The films are prepared by solvent
casting method and characterized by UV, FTIR studies. The films
were evaluated for disintegration time, Folding endurance, Tensile
Strength, Mouth dissolving time, Thickness, content uniformity and
In-vitro dissolution studies. The F5 formulation has given 98.5% drug
release within 6 minutes and has a tensile strength of 1.80 MPa.

The current study was aimed to develop the meclizine hydrochloride
sublimated fast dissolving tablets using different sublimated agents to
enhance the dissolution rate. The prepared fast dissolving tablets
were subjected to pre-compression properties and characterized for
hardness, weight variation, friability, wetting time, water absorption
ratio, and disintegration time. From In vitro dissolution studies, the
formulation F3 containing camphor (10%w/w) as the sublimating
agent showed rapid dissolution of about 98.61% in 30 min, and
disintegration time 43 sec when compared with other sublimating
agents. The percent drug release in 30 min (Q30) and initial
dissolution rate for formulation F3 was 98.61±0.25%, 3.29%/min.
These were very much higher compared to marketed tablets
(65.43±0.57%, 2.18%/min). The dissolution efficiency was found to
be 63.37 and it is increased by 1.4 fold with F3 FDT tablets
compared to marketed tablets. Differential scanning calorimetry and
Fourier transform infrared spectroscopy studies revealed that there
was no possibility of interactions. In conclusion, development of
meclizine hydrochloride fast dissolving tablets by sublimation
method is an appropriate method to enhance the dissolution rate.

Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication. Furanocoumarins’ defensive and restorative impacts have been observed in leukemia, glioma, breast, lung, renal, liver, colon, cervical, ovarian, and prostate malignancies. Experimental findings have shown that furanocoumarins activate multiple signaling pathways, leading to apoptosis, autophagy, antioxidant, antimetastatic, and cell cycle arrest in malignant cells. Additionally, furanocoumarins have been shown to have chemo preventiv...

Periodic mesoporous organosilica nanorods and nanospheres are synthesized from 1,4-bis(triethoxysilyl)ethylene and bis(3-ethoxysilylpropyl)disulfide. The nanosystems present the long-range order of the hexagonal nanostructure. They are degraded in simulated physiological conditions. The loading and release of doxorubicin with these nanosystems are both pH dependent. These nanoparticles are endocytosed by breast cancer cells and are very efficient for doxorubicin delivery in these cells.

Hardwickia  binata Roxb.  (Fabaceae)  root  bark  exudate  has  been
traditionally used by tribes of Chitteri hills to cure breast cancer. The
main  objective  of  this  study  is  to  give  a  scientific  validation  to  the
traditional use of  H. binata. The root bark exudates of  H. binatawas
collected  from  Chitteri  hills,  shade  dried,  coarsely  powdered  and
extracted  with  methanol  using  soxhlet  apparatus.  The  Physico
chemical  properties,  qualitative  phytochemical  studies,  quantitative
phytochemical  studies  and  GC-MS  analysis  was  carried  out.  The
cytotoxic  effect  of  methanol  extract  of  H.binata root  bark  exudate
was  studied  against  cancer  cell  lines  by  MTT  assay. The
phytochemical studies indicated the presence of flavonoids, saponins,
phenols and tannins. GC-MS study also revealed the  presence of 22
organic compounds out of which 18 compounds were reported with
various activities and five compounds reported to possess anticancer
activity.  In  vitro  cytotoxic  activity  on  the  cell  lines  showed  more
degree of inhibition against African Green Monkey Kidney Epithelial
cells  (Vero),  Human  cervical  cancer  cell  lines  (HeLa)  and  Human
breast cancer cells (MCF-7).

The present work was an attempt to investigate the potentialities of
multi-walled carbon nanotubes (MWCNT) as a carrier for targeting 6
Mercaptopurine to cancer tissues. MWCNTs were carboxy
functionalized and then loaded with 6 Mercaptopurine (6MP) using
the Incipient Wetness impregnation method to produce 6MP loaded
CNTs. The conjugate was characterized for drug loading efficiency,
in vitro drug release and release kinetics. The result indicated that a
maximum of about 65% entrapment was achieved. The loaded
nanotubes were shown to release the drug for more than 20 hours and
thus controlling the release. The release was found to follow the Zero
Order and Hixson Crowell release pattern. Our work established a
novel, easy to prepare formulation of MWCNTs with better drug
loading efficiency and increased dispersibility of CNTs and thus
improved bioavailability at cancer site with reduced systemic
toxicity.

ABSTRACT Impact of pH on the morphology of the Gold Nanoparticles (GNPs) synthesized using leaf extracts of Azadirachta indica is reported here. pH of the plant extract significantly affected the morphology of the GNPs. At pH 2 along with the formation of spherical GNPs, initiation of the non-spherical morphology also occurred. The non-spherical GNPs developed into more distinct gold nano-cubes when the pH of the plant extract was adjusted to pH 4. At pH 6, the optical as well as morphological features of the triangles, hexagons and plates became more conspicuous. It must be mentioned here that there were presence of some spherical GNPs also in each case that could have been an initiator of different morphologies directed by the pH of the reaction mixture. Presence of the dual absorption maxima confirmed the formation of non-spherical GNPs. Formation of spherical as well as non spherical nanoparticles such as gold nano-prisms and nano-hexagons was observed at pH 8. To confirm the possible involvement of nitrate reductase; its activity as a catalyst and /or template to navigate the formation of anisotropic GNPs is also depicted. It was found that the activity of the NR was drastically reduced after the formation of GNPs.

The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong gram-positive and -negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of non-natural analogs.

Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication. Furanocoumarins' defensive and restorative impacts have been observed in leukemia, glioma, breast, lung, renal, liver, colon, cervical, ovarian, and prostate malignancies. Experimental findings have shown that furanocoumarins activate multiple signaling pathways, leading to apoptosis, autophagy, antioxidant, antimetastatic, and cell cycle arrest in malignant cells. Additionally, furanocoumarins have been shown to have chemo preventive and chemotherapeutic synergistic potential when used in combination with other anticancer drugs. Here, we address different pathways which are activated by furanocoumarins and their therapeutic efficacy in various tumors. Ideally, this review will trigger interest in furanocoumarins and their potential efficacy and safety as a cancer lessening agents.

A new nanohydrogel drug delivery platform based on Laponite nanodiscs, polyacrylate, and sodium phosphate salts is described. The hybrid nanohydrogel is tailored to obtain soft and flexible nanohydrogels with G′ around 3 kPa, which has been proposed as the ideal stiffness for drug delivery applications. In vitro studies demonstrate that the new nanohydrogels are biocompatible, biodegradable, nonswellable, pH-responsive, and noncytotoxic and are able to deliver antineoplastic drugs into cancer cells. The IC 50 of nanohydrogels containing cisplatin, 4-fluorouracil, and cyclo-phosphamide is significantly lower than the IC 50 of the free drugs. In vivo experiments suggest that the new nanomaterials are biocompatible and do not accumulate in crucial organs. The simple formulation procedure enables encapsulation of virtually any water-soluble molecule, without the need for chemical modification of the guests. These nanohydrogels are a versatile platform that enables the simultaneous encapsulation of several cancer drugs, yielding an efficient drug cocktail delivery system, which for instance presents a positive synergistic effect against MCF-7 cells.

Quinazoline scaffold has been successfully utilized for development of various inhibitors of tubulin, epidermal growth factor receptor (EGFR), polo like kinases (PLKs), Hedgehog-Gli signaling pathway and protein kinase B (PKB) /Akt pathway. Compounds based on quina-zolines have shown efficacies in M to nM range in various cancer cell lines and thus could be useful scaffolds for development of both apoptosis inducers as well as inhibitors. This compilation is based on various patents published till 2015 and divides the quinazolines in two main categories: Quinazolines as apoptosis inducers and as apoptosis inhibitors. These two main categories are further subcategorized based on the use/pharmacological indications for these classes of patented compounds. This review will act as a tool for the researchers working on exploring the anticancer potential of quinazoline as a privileged heterocyclic. The promising anticancer profile of some of the quinazoline based compounds clearly highlights the clinical potential of this heterocycle.

Cancer has become a serious concern in public health. Harmful side effects and multidrug resistance of traditional chemotherapy have prompted urgent needs for novel anticancer drugs or therapeutic approaches. Anticancer peptides (ACPs) have become promising molecules for novel anticancer agents because of their unique mechanism and several extraordinary properties. Most α-helical ACPs target the cell membrane, and interactions between ACPs and cell membrane components are believed to be the key factor in the selective killing of cancer cells. In this review, we focus on the exploitation of the structure and function of α-helical ACPs, including the distinction between cancer and normal cells, the proposed anticancer mechanisms, and the influence of physicochemical parameters of α-helical ACPs on the biological activities and selectivity against cancer cells. In addition, the design and modification methods to optimize the cell selectivity of α-helical ACPs are considered. Furthermore, the suitability of ACPs as cancer therapeutics is discussed.

An ideal nanocarrier for efficient drug delivery must be able to target specific cells and carry high doses of therapeutic drugs and should also exhibit optimized physicochemical properties and biocompatibility. However, it is a tremendous challenge to engineer all of the above characteristics into a single carrier particle. Here, we show that natural H-ferritin (HFn) nanocages can carry high doses of doxorubicin (Dox) for tumor-specific targeting and killing without any targeting ligand functionalization or property modulation. Dox loaded
HFn (HFn-Dox) specifically bound and subsequently internalized into tumor cells via interaction with overexpressed transferrin receptor 1 and released Dox in the lysosomes. In vivo in the mouse, HFn-Dox exhibited more than 10-fold higher intratumoral drug concentration
than free Dox and significantly inhibited tumor growth
after a single-dose injection. Importantly, HFn-Dox displayed an excellent safety profile that significantly reduced healthy organ drug exposure and improved the maximum tolerated dose by fourfold compared with free Dox. Moreover, because the HFn nanocarrier has well-defined morphology and does not need any ligand modification or property modulation it can be easily produced with high purity and yield, which are requirements for drugs used in clinical trials. Thus, these unique properties make the HFn nanocage an ideal vehicle for efficient anticancer drug delivery.

Apoptosis is a form of cell death that permits the removal of damaged, senescent or unwanted cells in multicellular organisms, without damage to the cellular microenvironment, but it is also involved in a wide range of pathological processes, including cancer. An understanding of the underlying mechanism of apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. Defective apoptosis represents a major causative factor in the development and progression of cancer. The majority of chemotherapeutic agents, as well as radiation, utilize the apoptotic pathway to induce cancer cell death. Recent knowledge on apoptosis has provided the basis for novel targeted therapies that exploit apoptosis to treat cancer by acting in the extrinsic/intrinsic pathway. Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. In particular, this review provides references concerning the apoptotic molecules, their interactions, the mechanisms involved in apoptosis resistance, and also the modulation of apoptosis for the treatment of cancer. Despite being the cause of problem, apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. Get more articles at: http://www.innspub.net/volume-2-number-3-june-2012/

The efficacy of classical and molecular therapies in cancer is hampered by the occurrence of primary (intrinsic) and secondary (acquired) refractoriness of tumours to selected therapeutic regimens. Nevertheless, the increased knowledge of the genetic, molecular and metabolic mechanisms underlying cancer results in the generation of a correspondingly increasing number of druggable targets and molecular drugs. Thus, a current challenge in molecular oncology and medicinal chemistry is to cope with the increased need for modelling, both in cellular and animal systems, the genetic assets associated to cancer resistance to drugs. In this review, we summarize the current strategies for generation and analysis of in vitro and in vivo models, which may reveal useful to extract information on the molecular basis of intrinsic and acquired resistance to anticancer molecular agents.

Semiconductor quantum dots (QDs) are favorite candidates for many applications especially for potential use as optical bioimaging agents. But the major issue of QDs is toxicity. In the present study, carbon nanodots were synthesized using a green hydrothermal approach from gelatin protein using a previously established protocol. However, the PL properties and applications of the as-synthesized CG (bovine gelatin) nanodots were remarkably different from those of previously reported gelatin carbon dots. CG (bovine gelatin) nanodots had sizes greater than the Bohr exciton radius but still had QD like fluorescence characteristics. Furthermore, the results from fluorescence spectroscopy demonstrated a tunable PL emission profile at various excitation wavelengths. Second, carbon nanodots were also synthesized from algal biomass of Pectinodesmus sp. via a green hydrothermal approach, denoted as CA (PHM3 algae) nanodots. A study of the PL properties and surface chemical composition of CG (bovine gelatin) and CA (PHM3 algae) nanodots suggested that the surface chemical composition significantly alters the surface states which directly influence their PL properties. CG (bovine gelatin) nanodots were used for imaging of plant and bacterial cells with good imaging sensitivity comparable to toxic semiconductor quantum dots. Moreover, the results from in vitro studies suggested good anticancer properties of CA (PHM3 algae) and CG (bovine gelatin) nanodots with minimum GI50 values of 0.316 AE 0.447 ng ml À1 (n ¼ 2) and 8.156 AE 6.596 ng ml À1 (n ¼ 2) for HCC 1954 (breast cancer) and 0.542 AE 0.715 ng ml À1 (n ¼ 2) and 23.860 AE 14.524 ng ml À1 (n ¼ 2) for HCT 116 (colorectal cancer) cell lines, respectively.

As a fascinating alternative to overcome the undesired side effects and to improve therapeutic efficacy and water solubility of chemotherapeutic agent tamoxifen (TAM), the simplistic method based on folic acid (FA) tagged amphiphilic graphene oxide (GO) for cell specific delivery was adopted. Besides, FA-GO also served as template for synthesis of Ag NP. Hence, the present study demonstrates a co-delivery system for folate receptor (FR) targeted delivery of anticancer agents TAM and Ag NP for combination therapeutics of breast cancer in vitro. The method involved the syntheses of sulfonate modified GO with FA functionalization which was validated by FTIR and UV-vis analysis. TAM was loaded onto the FA-GO nanocarrier by physi-osorption of hydrophobic drug onto surface with encapsula-tion efficiency (EE) around 98 %. The synthesized FA-GO@AgNP@TAMnanocarrier was physiologically stable with average zeta potential and hydrodynamic size ofÀ40 mV, 167 nm contrarily to alone GO withÀ29.5 mV, 5 nm respectively. Cellular uptake studies revealed specificity of nano-carrier towards FR (+ ve) breast carcinoma (MCF-7 cell line) compared to FR (-ve) lung carcinoma (A549 cell line). Based on cell specificity of nanocarrier, the cytotoxicity of various nano-carrier combinations was investigated towards MCF-7 cells. The combination exhibited superior cytotoxic effect than TAM, Ag NP alone at relatively lower concentrations with notable cell cycle growth arrest in sub-G 1 phase. The FA-GO@AgNP@TAMna-nocarrier showed elevated intracellular reactive oxygen species (ROS) generation with considerable dissipation of mitochon-drial membrane potential (MMP). Furthermore the semi-quantitative RT-PCR analysis showed increased pro-apoptotic genes expression with highest expression of caspase-3. Altogether the study suggests mitochondria mediated apoptotic signaling pathway. These findings suggest the above designed nano-carrier could serve as the potential candidate for targeted combination breast cancer therapy.

This work evaluated under accelerated conditions the stability of the
biodegradable gentamicin-glyceryl monooleate water based-gel used
in the treatment of chronic osteomyelitis. Three batches of 600.0 g of
gentamicin -glyceryl monooleate -water based-gel (5/80/15% w/w)
were manufactured. The samples were stored in a climatic test
chamber for stability evaluation according to the standards published
by the International Conference on Harmonisation and the World
Health Oganization (25 ± 2°C / 60 ± 5%RH) for 6 months. Samples
were evaluated at pre-determinate times 0, 3 and 6 months with
regard to their physicochemical properties and In Vitro drug release
characteristics. Gentamicin sulfate present in the freshly prepared
gels was the same after three and six months of storage at 25°C / 60%
RH. However the relative amount of gentamicin sulfate in the freshly
prepared gel that was about 110% decreased by about 11% after six
months of storage. The release profiles of the gels remained similar
despite a partial hydrolysis of glyceryl monooleate and an increase in
the residual amount of water and in the viscosity.

Tumor resistance to cytotoxic chemotherapy drugs and their toxicity to normal cells are major clinical obstacles to anticancer therapy effectiveness. Alterations in various DNA repair pathways play a key role in the development of both mechanisms of drug resistance and toxicity. Since deregulation of the DNA damage response and alterations in DNA repair pathways are relatively common in human cancer, the knowledge of these alterations in cancer cells would be an important predictive factor for the clinical response to che-motherapy and a useful guide in designing an appropriate therapeutic strategy. This review is focused on the mismatch repair (MMR) pathway and the O 6-methylguanine-DNA-methyltransferase (MGMT) repair protein. In particular, we examine how inactivation of these DNA repair mechanisms might affect the response of tumor cells to chemother-apy, with a special emphasis on agents inducing methylation and oxidative DNA damage and interstrand DNA cross-links (ICLs). In addition , we provide novel experimental evidence indicating that MMR is required for efficient repair of ICLs via stabilization of RAD51 containing repair intermediates. Finally, we discuss possible emerging therapeutical strategies for treating MMR-defective tumors. INTRODUCTION The resistance of cancer cells to chemotherapeutic drugs and the toxicity of these drugs to normal cells are both obstacles to the successful treatment of cancer. Resistance can be due to altered drug accumulation, retention, metabolism and distribution or to aberrant processing of drug-induced DNA damage. Because most common anticancer drugs are essentially non-selective, effective doses are often associated with severe toxicity. The development of novel anticancer drugs with low toxicity for dividing normal host tissues is a major goal. Recent results from mouse cancer models have raised questions regarding the relevance of targeting DNA repair and cell cycle defects for cancer therapy. Deregulation of the DNA damage response and alterations in DNA repair pathways are frequently associated with tumor development. In addition, pathways that control cell cycle progression, DNA repair or cell death have been shown to play an important role in the regulation of cellular resistance to anticancer drugs.

The aim of this review is to provide an understanding of the anatomical and histological structure of the nasal cavity, which is important for nasal drug and vaccine delivery as well as the development of new devices. The surface area of the nasal cavity is about 160 cm2, or 96 m2 if the microvilli are included. The olfactory region, however, is only about 5 cm2 (0.3 m2 including the microvilli). There are 6 arterial branches that serve the nasal cavity, making this region a very attractive route for drug administration. The blood flow into the nasal region is slightly more than reabsorbed back into the nasal veins, but the excess will drain into the lymph vessels, making this region a very attractive route for vaccine delivery. Many of the side effects seen following intranasal administration are caused by some of the 6 nerves that serve the nasal cavity. The 5th cranial nerve (trigeminus nerve) is responsible for sensing pain and irritation following nasal administration but the 7th cranial nerve (facial nerve) will respond to such irritation by stimulating glands and cause facial expressions in the subject. The first cranial nerve (olfactory nerve), however, is the target when direct absorption into the brain is the goal, since this is the only site in our body where the central nervous system is directly expressed on the mucosal surface. The nasal mucosa contains 7 cell types and 4 types of glands. Four types of cells and 2 types of glands are located in the respiratory region but 6 cell types and 2 types of glands are found in the olfactory region.

In the present investigation, curcumin loaded magnetically active frustules have been
reported. The diatoms were cultured and frustules were obtained by chemical and thermal
process. The frustules were rendered magnetically active by incorporation of iron oxide
nanoparticle using two different method involving ferrofluid (CMDM-F) and in situ synthesis
(CMDM-I) of iron oxide nanoparticle. These CMDM prepared by two techniques were
characterized using FT-IR and vibrating sample magnetometer (VSM) analysis. Particle size
and potential were measured using the Malvern Zetasizer. Scanning electron microscopy
(SEM) was utilized for studying the surface morphology of CMDM, and in addition to this
elemental analysis was also performed for confirming the presence of iron. The cell viability
assay was carried out using the HeLa cell line. SEM images showed a change in surface
morphology of diatoms before and after rendering magnetic activity. Cell viability assay
revealed that CMDM-F had reasonably high cytotoxicity (60.2%) compared to Curcumin
(42.1%), DM (1.9%), CDM (44.8%), CMDM-I (59.9). Both, CMDM-F and CMDM-I
showed improved cytotoxicity when compared with pure curcumin. The overall study
suggests that the developed CMDM could be utilized as a potential carrier to deliver cargo
for efficient chemotherapy.