Anticancer Drug Delivery

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.

In the present work, a series of 0, 1 and 7 wt% silver nano-particles (Ag NPs) incorporated poly lactic-co-glycolic acid (PLGA) nano-fibers were synthesized by the electrospinning process. The PLGA/Ag nano-fibers sheets were characterized using SEM, TEM and DSC analyses. The three synthesized PLGA/silver nano-fiber composites were screened for anticancer activity against liver cancer cell line using MTT and LDH assays. The anticancer activity of PLGA nano-fibers showed a remarkable improvement due to increasing the concentration of the Ag NPs. In addition to the given result, PLGA nano-fibers did not show any cytotoxic effect. However, PLGA nano-fibers that contain 1 % nano silver showed anticancer activity of 8.8 %, through increasing the concentration of the nano silver to 7 % onto PLGA nano-fibers, the anticancer activity was enhanced to a 67.6 %. Furthermore, the antibacterial activities of these three nano-fibers, against the five bacteria strains namely; E.coli o157:H7 ATCC 51659, Staphylococcus aureus ATCC 13565, Bacillus cereus EMCC 1080, Listeria monocytogenes EMCC 1875 and Salmonella typhimurium ATCC25566 using the disc diffusion method, were evaluated. Sample with an enhanced inhibitory effect was PLGA/Ag NPs (7 %) which inhibited all strains (inhibition zone diameter 10 mm); PLGA/Ag NPs (1 %) sample inhibited only one strain (B. cereus) with zone diameter 8 mm. The PLGA nano-fiber sample has not shown any antimicrobial activity. Based on the anticancer as well as the antimicrobial results in this study, it can be postulated that: PLGA nanofibers containing 7 % nano silver are suitable as anticancer- and antibiotic-drug delivery systems, as they will increase the anticancer as well as the antibiotic drug potency without cytotoxicity effect on the normal cells. These findings also suggest that Ag NPs, of the size (5–10 nm) evaluated in the present study, are appropriate for therapeutic application from a safety standpoint.

Water soluble CdS nanoparticles were synthesized by reacting CdCl2 with sodium thiosulphate solutions as sulphur precursor. The facile one-pot synthetic route produced tunable (2-10 nm) high quality QDs with narrow particle size distribution and enhanced quantum yields (QY).

Extracts from 27 marine algal species (14 Rhodophyta, 5 Phaeophyta, and 8 Chlorophyta) from the Yucatán Peninsula
(Mexico) were evaluated for cytotoxic and antiproliferative activity by 3(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) and sulforhodamine B (SRB) assays, respectively. To determine the specificity of cytotoxic activity against tumor cells, the selective index (SI) was also calculated. The following cancer cell lines were employed: normal canine kidney (MDCK) cells, human laryngeal carcinoma (Hep-2) cells, human cervical adenocarcinoma (HeLa) cells, and human nasopharyngeal carcinoma (KB) cells. The results indicated that 44% and 51% of the algal species tested showed cytotoxic and antiproliferative activity, respectively. Most of the cytotoxic extracts were from species of Chlorophyta, with Udotea flabellum and U. conglutinate showing the highest cytotoxic activity against all the cancer cell lines. For Rhodophyta, the Bryothamnion triquetrum extract showed outstanding selective cytotoxicity against Hep-2 cells (CC50 8.29 μg mL–1, SI = 12.04). Two of the
five species of Phaeophyta tested (Lobophora variegata and Dictyota caribaea) showed high cytotoxicity activity against the
KB cell line. The data show that these species are a potential source of compounds for the treatment of certain cancer diseases.

The aim of this study was to investigate the stability of four corticosteroids in the presence of human colonic bacteria to understand better their luminal behaviour when delivered orally in the treatment of inflammatory bowel disease. The stability of prednisolone, budesonide, beclometasone (17, 21) dipropionate (BDP) and its active metabolite, beclometasone-17-monopropionate (17-BMP), were investigated at three different concentrations following incubation in a mixed faecal inoculum (simulated human colonic fluid) under anaerobic conditions. Prednisolone, at all three concentrations, was completely degraded within 3 h. The degradation of budesonide progressed at a slower rate, with complete degradation occurring within 7h; the degradation of the S epimer of budesonide was faster than the R epimer. BDP degraded completely within 2 h while its active metabolite 17-BMP was comparatively stable. In contrast to the results in the faecal inoculum, all molecules were stable in the simula...

Modelling of the quantum interaction properties of nitrone on the fullerene C60 has been investigated by the use of PM3 calculations. It has been found that the interaction potential of the nitrone with the fullerene C60 led to stable complexes when the fullerene reacted with the carbon atom (C 1-centered) and metastable conformations with carbon atom (C 2-centered). We have studied the eect of two rotation characteristics (nitrone and NOCH2 group) on the binding between the fullerene C60 with the nitrone. Our results suggested that the binding energy is lower as the nitrone rotation increases and the NOCH2 group rotation showed more eect. The fullerene C60 may be able to do more linking with molecules of nitrone.

Vascular endothelial growth factor receptor (VEGFR) is an important receptor tyrosine kinase (RTK) in the induction of angiogenesis. Abnormal activation of VEGFR leads to several disorders including cancer. Nowadays, inhibition of VEGFR kinase has been one of the most powerful clinical strategies in cancer treatment and great efforts to design and synthesize small molecular VEGFR inhibitors for cancer research have been made in recent years. This review highlights the major progress and development of them, including their structure and pharmacophore features, biological activities and structure-activity relationships (SAR). Special attentions are paid to the compounds available in market or in advanced clinical stages.

The small intestine is the primary site of absorption for many drugs administered orally and so is the target tissue for pharmacotherapeutic strategies to control the oral absorption of drugs. Drug transporters, including the ATP-binding cassette (ABC) superfamily and the solute carrier (SLC) superfamily, have been considered to play a physiological role in regulating the absorption of xenobiotics, and variations in their expression level and function in the small intestine cause intra- and inter-individual variation in the oral absorption of drugs. Recent advances in molecular biology have suggested that genetic polymorphisms are associated with the expression level and function, and thereby inter-individual variation. In this review, the pharmacogenetics of these transporters is summarized, and their future significance in the clinical setting is discussed.

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 of nanohydrogels containing cisplatin, 4-fluorouracil, and cyclophosphamide is significantly lower than the IC 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 encapsul...

Modelling of the quantum interaction properties of nitrone on the fullerene C60 has been investigated by the use of PM3 calculations. It has been found that the interaction potential of the nitrone with the fullerene C60 led to stable complexes when the fullerene reacted with the carbon atom (C1-centered) and metastable conformations with carbon atom (C2-centered). We have studied the eect of two rotation characteristics (nitrone and NOCH2 group) on the binding between the fullerene C60 with the nitrone. Our results suggested that the binding energy is lower as the nitrone rotation increases and the NOCH2 group rotation showed more eect. The fullerene C60 may be able to do more linking with molecules of nitrone.

20-(S)-Camptothecin (CPT)-conjugated dipeptides are reported that preassemble into nanotubes with diameters ranging from 80-120 nm. These nanoassemblies maintain a high (∼47 %) drug loading and exhibit greater drug stability (i.e., resistance to lactone hydrolysis), and consequently greater efficacy against several human cancer cells (HT-29, A549, H460, and H23) in vitro compared with the clinically used prodrug irinotecan. A key and defining feature of this system is the use of the CPT-conjugated dipeptide as both the drug and precursor to the nanostructured carrier, which simplifies the overall fabrication process.

Oxaliplatin loaded PLAGA microspheres have been prepared by solvent extraction process. Parameters affecting the release kinetics in vitro have been studied in order to design specific release profiles suitable for direct intra-tumoral injection. By varying the nature and the relative proportions of different polymers we managed to prepare microspheres with good encapsulation efficiency (75-90%) and four different release profiles: zero order kinetics (type II) and the classical sigmoïd release profile with three different sizes of plateau and burst. These results, if correlated with in vivo activity, are promising to enhance effectiveness of local tumor treatment.