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Mohandas A, Kumar PT S, Raja B, et al. Int J Nanomedicine. 2015;10(Suppl 1):53–66. The authors have advised that Figure 8B and C (page 62) were incorrect in the original manuscript, as the Alginate control group is inadvertently repeated in the Alginate +0.1% nZnO group. Due to this mistake they have repeated the entire cell attachment studies using DAPI. The authors have confirmed that this does not in any way affect the conclusions from Figure 8B and C, and that it is not going to affect the overall conclusionof this published paper. They apologize for any inconvenience. The correct version of Figure 8 is presented below. Read the original article

Annapoorna Mohandas,* Sudheesh Kumar PT,* Biswas Raja, Vinoth-Kumar Lakshmanan, Rangasamy Jayakumar Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi, India *These authors contributed equally to this work Abstract: Alginate hydrogel/zinc oxide nanoparticles (nZnO) composite bandage was developed by freeze-dry method from the mixture of nZnO and alginate hydrogel. The developed composite bandage was porous with porosity at a range of 60%–70%. The swelling ratios of the bandages decreased with increasing concentrations of nZnO. The composite bandages with nZnO incorporation showed controlled degradation profile and faster blood clotting ability when compared to the KALTOSTAT® and control bandages without nZnO. The prepared composite bandages exhibited excellent antimicrobial activity against Escherichia coli, Staphylococcus aureus, Candida albicans, and methicillin resistant S. aureus (MRSA). Cytocompatibility evaluation of the prepared composite bandages done on human dermal fibroblast cells by Alamar assay and infiltration studies proved that the bandages have a non-toxic nature at lower concentrations of nZnO whereas slight reduction in viability was seen with increasing nZnO concentrations. The qualitative analysis of ex-vivo re-epithelialization on porcine skin revealed keratinocyte infiltration toward wound area for nZnO alginate bandages. Keywords: alginate, hydrogel, ZnO nanoparticle, hemostatic, antimicrobial activity, wound healing

Biomarkers are molecules such as proteins, genes, or other substances that may be tested to determine the stage of the tumor in a patient. The role of prostate cancer biomarkers is pivotal and the combination of prostate cancer immunotherapy with efficient biomarkers has emerged as a beneficial treatment strategy and its use has increased rapidly. The two primary objectives of this current prostate cancer early detection programs were recognizing non-symptomatic individuals with prostate cancer requiring prostatic core biopsy and identifying men with prostate cancer who might benefit from definitive medical treatment. The progress that has been made so far in the identification of the biomarkers that can be used for the classification, prediction and prognostication of prostate cancer, and as major targets for its clinical intervention has been well summarized in this review., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Nanogels offer hope for precise drug delivery, while addressing drug delivery hurdles is vital for effective prostate cancer (PCa) management. We developed an injectable elastin nanogels (ENG) for efficient drug delivery system to overcome castration-resistant prostate cancer (CRPC) by delivering Decursin, a small molecule inhibitor that blocks Wnt/βcatenin pathways for PCa. The ENG exhibited favourable characteristics such as biocompatibility, flexibility, and low toxicity. In this study, size, shape, surface charge, chemical composition, thermal stability, and other properties of ENG were used to confirm the successful synthesis and incorporation of Decursin (DEC) into elastin nanogels (ENG) for prostate cancer therapy. In vitro studies demonstrated sustained release of DEC from the ENG over 120 h, with a pH-dependent release pattern. DU145 cell line induces moderate cytotoxicity of DEC-ENG indicates that nanomedicine has an impact on cell viability and helps strike a balance between therapeutics efficacy and safety while the EPR effect enables targeted drug delivery to prostate tumor sites compared to free DEC. Morphological analysis further supported the effectiveness of DEC-ENG in inducing cell death. Overall, these findings highlight the promising role of ENG-encapsulated decursin as a targeted drug delivery system for CRPC., (© 2024. The Author(s).)

The development of new therapeutic strategies is on the increase for prostate cancer stem cells, owing to current standardized therapies for prostate cancer, including chemotherapy, androgen deprivation therapy (ADT), radiotherapy, and surgery, often failing because of tumor relapse ability. Ultimately, tumor relapse develops into advanced castration-resistant prostate cancer (CRPC), which becomes an irreversible and systemic disease. Hence, early identification of the intracellular components and molecular networks that promote prostate cancer is crucial for disease management and therapeutic intervention. One of the potential therapeutic methods for aggressive prostate cancer is to target prostate cancer stem cells (PCSCs), which appear to be a primary focal point of cancer metastasis and recurrence and are resistant to standardized therapies. PCSCs have also been documented to play a major role in regulating tumorigenesis, sphere formation, and the metastasis ability of prostate cancer with their stemness features. Therefore, the current review highlights the origin and identification of PCSCs and their role in anti-androgen resistance, as well as stemness-related signaling pathways. In addition, the review focuses on the current advanced therapeutic strategies for targeting PCSCs that are helping to prevent prostate cancer initiation and progression, such as microRNAs (miRNAs), nanotechnology, chemotherapy, immunotherapy, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing system, and photothermal ablation (PTA) therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ramesh, Selvakumar, Ameer, Lian, Abdullah Alzarooni, Ojha, Mishra, Tiwari, Kaushik, Jung, Chouaib and Lakshmanan.)

Piperine, a natural alkaloidal pungent product present in pepper plants, possesses the properties of anti-inflammatory and anti-metastasis. Lithocholic acid is a monohydroxy-5beta-cholanic acid with an alpha-hydroxy substituent at position 3; it is a secondary bile acid that plays a pivotal role in fat absorption, and has been discovered to mediate colorectal cancer (CRC) cell invasion and migration. However, the effect of piperine on angiogenesis has been poorly investigated. In the current study, we examined the role of piperine on LCA-stimulated angiogenesis by measuring interleukin-8 (IL-8) expression; moreover, we revealed the potential molecular mechanisms in CRC cells. Here, we showed that piperine inhibited LCA-stimulated endothelial EA.hy926 cell angiogenesis in a conditioned medium obtained from colorectal HCT-116 cells. Experiments with an IL-8 neutralizer showed that IL-8 present in the conditioned medium was the major angiogenic factor. Piperine inhibited LCA-stimulated ERK1/2 and AKT via the Src/EGFR-driven ROS signaling pathway in the colorectal cell line (HCT-116). Through mutagenesis and inhibitory studies, we revealed that ERK1/2 acted as an upstream signaling molecule in AP-1 activation, and AKT acted as an upstream signaling molecule in NF-κB activation, which in turn attenuated IL-8 expression. Taken together, we demonstrated that piperine blocked LCA-stimulated IL-8 expression by suppressing Src and EGFR in human CRC HCT-116 cells, thus remarkably attenuating endothelial EA.hy926 cell tube formation.

The combination of cancer immunotherapy with efficient functionalized nanosystems has emerged as a beneficial treatment strategy and its use has increased rapidly. The roles of stimuli-responsive nanosystems and nanomedicine-based cancer immunotherapy, a subsidiary discipline in the field of immunology, are pivotal. The present era is witnessing rapid advancements in the use of nanomedicine as a platform for investigating novel therapeutic applications and modern intelligent healthcare management strategies. The development of cancer nanomedicine has posthaste ratified the outcomes of immunotherapy to the subsequent stage in the current era of medical research. This review focuses on key findings with respect to the effectiveness of nanomedicine-based cancer immunotherapies and their applications, which include i) immune checkpoint inhibitors and nanomedicine, ii) CRISPR-Cas nanoparticles (NPs) in cancer immunotherapy, iii) combination cancer immunotherapy with core-shell nanoparticles, iv) biomimetic NPs for cancer immunotherapy, and v) CAR-T cells and cancer nanoimmunotherapy. By evaluating the state-of-the-art tools and taking the challenges involved into consideration, various aspects of the proposed nano-enabled therapeutic approaches have been discussed in this review., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc. part of Springer Nature.)

In the present study, we assessed whether nootkatone (NKT), a sesquiterpene in edible plants, can provide protection against dyslipidemia, intramyocardial lipid accumulation, and altered lipid metabolism in a rat model of myocardial infarction (MI) induced by subcutaneous injections of isoproterenol (ISO, 85 mg/kg) on days 9 and 10. The rats were pre- and co-treated with NKT (10 mg/kg, p.o.) administered daily for 11 days. A significant reduction in the activities of myocardial creatine kinase and lactate dehydrogenase, as well as non-enzymatic antioxidants, and alterations in lipids and lipoproteins, along with a rise in plasma lipid peroxidation and intramyocardial lipid accumulation, were observed in ISO-treated rats. ISO administration induced alterations in the activities of enzymes/expressions that played a significant role in altering lipid metabolism. However, NKT treatment favorably modulated all biochemical and molecular parameters altered by ISO and showed protective effects against oxidative stress, dyslipidemia, and altered lipid metabolism, attributed to its free-radical-scavenging and antihyperlipidemic activities in rats with ISO-induced MI. Additionally, NKT decreased the accumulation of lipids in the myocardium as evidenced from Oil red O staining. Furthermore, the in vitro observations demonstrate the potent antioxidant property of NKT. The present study findings are suggestive of the protective effects of NKT on dyslipidemia and the underlying mechanisms. Based on our findings, it can be suggested that NKT or plants rich in NKT can be promising for use as a phytopharmaceutical or nutraceutical in protecting the heart and correcting lipid abnormalities and dyslipidemia, which are risk factors for ischemic heart diseases.

Urokinase-type plasminogen activator receptor (uPAR) plays a crucial role in inflammation and tumor metastasis. Docosahexaenoic acid (DHA), a representative omega-3 polyunsaturated fatty acid, has been shown to exhibit anti-inflammatory and anti-tumor properties. However, the mechanism by which DHA negatively regulates uPAR expression is not yet understood. The aim of this study was to investigate the effect of DHA on 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced uPAR expression and potential role of heme oxygenase-1 (HO-1) in DHA-induced inhibition of uPAR in human endothelial ECV304 cells. Results showed that TPA induced uPAR expression in a time dependent manner, while DHA inhibited uPAR expression in a concentration-dependent manner. Moreover, treatment with DHA induced HO-1 expression in a time- and concentration-dependent manner. In addition, DHA-induced inhibition of uPAR expression and cell invasion in TPA-stimulated cells was reversed by si-HO-1 RNA. Induction of HO-1 by ferric protoporphyrin IX (FePP) inhibited TPA-induced uPAR expression, and this effect was abolished by treatment with the HO-1 inhibitor tin protoporphyrin IX (SnPP). Additionally, carbon monoxide, an HO-1 product, attenuated TPA-induced uPAR expression and cell invasion. Collectively, these data suggest a novel role of DHA-induced HO-1 in reducing uPAR expression and cell invasion in human endothelial ECV304 cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Lian, Li, Sah, Kim, Lakshmanan and Jung.)

The present era is witnessing rapid advancements in the field of medical informatics and modern healthcare management. The role of translational bioinformatics (TBI), an infant discipline in the field of medical informatics, is pivotal in this revolution. The development of high-throughput technologies [e.g., microarrays, next-generation sequencing (NGS)] has propelled TBI to the next stage in this modern era of medical informatics. In this review, we assess the promising translational outcomes of microarray- and NGS-based discovery of genes, proteins, micro RNAs, and other active biological compounds aiding in the diagnosis, prognosis, and therapy of prostate cancer (PCa) to improve treatment strategies at the localized and/or metastatic stages in patients. Several promising candidate biomarkers in circulating blood (miR-25-3p and miR-18b-5p), urine (miR-95, miR-21, miR-19a, and miR-19b), and prostatic secretions (miR-203) have been identified. AURKA and MYCN, novel candidate biomarkers, were found to be specifically expressed in neuroendocrine PCa. The use of BTNL2 gene mutations and inflammasomes as biomarkers in immune function-mediated, inherited PCa has also been elucidated based on NGS data. Although TBI discoveries can benefit clinical performance metrics, the translational potential and the in vivo performance of TBI outcomes need to be verified. In conclusion, TBI aids in the effective clinical management of PCa; furthermore, the fate of personalized/precision medicine mostly relies on the enhanced diagnostic, prognostic, and therapeutic potential of TBI., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

DNA nanotechnology has laid a platform to construct a variety of custom-shaped nanoscale objects for functionalization of specific target materials to achieve programmability and molecular recognition. Herein, we prepared DNA nanostructures [namely, synthetic DNA rings (RDNA) and DNA duplexes extracted from salmon (SDNA)] containing metal ions (M 2+ ) such as Cu 2+ , Ni 2+ , and Zn 2+ as payloads for delivery to exterminate highly pathologic hospital bacterial strains (e.g., Escherichia coli and Bacillus subtilis) and prostate cancer cells (i.e., PC3, LNCaP, TRAMP-C1, 22Rv1, and DU145). Morphologies of these M 2+ -doped RDNA were visualized using atomic force microscopy. Interactions between M 2+ and DNA were studied using UV-vis and Fourier transform infrared spectroscopy. Quantitative composition and chemical changes in DNA without or with M 2+ were obtained using X-ray photoelectron spectroscopy. In addition, M 2+ -doped DNA complexes were subjected to antibacterial activity studies. They showed no bacteriostatic or bactericidal effects on bacterial strains used. Finally, in vitro cellular toxicity study was conducted to evaluate the effect of pristine DNA and M 2+ -doped DNA complexes on prostate cancer cells. Cytotoxicities conferred by M 2+ -doped DNA complexes for most cell lines were significantly higher than those of M 2+ without DNA. Cellular uptake of these complexes was confirmed by fluorescence microscopy using PhenGreen FL indicator. On the basis of our observations, DNA nanostructures can be used as safe and efficient nanocarriers for delivery of therapeutics. They have enhanced therapeutic window than bare metals.

DNA nanotechnology can be used to create intricate DNA structures due to the ability to direct the molecular assembly of nanostructures through a bottom-up approach. Here, we propose nanocarriers composed of both synthetic and natural DNA for drug delivery. The topological, optical characteristics, and interaction studies of Cu 2+ /Ni 2+ /Zn 2+ -curcumin-conjugated DNA complexes were studied using atomic force microscopy (AFM), UV-vis spectroscopy, Fourier transform infrared and mass spectroscopy. The maximum release of metallo-curcumin conjugates from the DNA complexes, triggered by switching the pH, was found in an acidic medium. The bacterial growth curves of E. coli and B. subtilis displayed a prolonged lag phase when tested with the metallo-curcumin-conjugated DNA complexes. We also tested the in vitro cytotoxicity of the metallo-curcumin-conjugated DNA complexes to prostate cancer cells using an MTS assay, which indicated potent growth inhibition of the cells. Finally, we studied the cellular uptake of the complexes, revealing that DNA complexes with Cu 2+ /Ni 2+ -curcumin exhibited brighter fluorescence than those with Zn 2+ -curcumin.

Oxide nanoparticles have numerous potential applications in medicine such as carriers for therapeutic drugs, contrast agents for bio-imaging and targeting agents for tumors. Oxide nanoparticles may also have an inherent cytotoxicity towards cancer cells, as recently found for cerium oxide. KNbO3 nanoparticles have a combination of low toxicity and nonlinear optical properties which make them attractive for use as a bio-imaging material. However, little is known yet about the cytotoxicity of KNbO3 particles towards cancerous cells. In the present work, the cytotoxicity of KNbO3 particles to normal and prostate cancer cell lines is studied. The mixed oxide method is used to prepare KNbO3 powder. Using dynamic light scattering the mean particle diameter of the KNbO3 powder is found to be ∼500 nm. X-ray diffraction, Fourier transform infra-red spectroscopy and Raman scattering spectroscopy are used to examine the structure of the KNbO3 powder. Powder morphology is examined using scanning electron microscopy. MTT assays of EA.hy926, PC-3 and DU-145 cell lines are carried out to study cell-specific cytotoxicity. KNbO3 sub-micron particles are found to have low toxicity to PC-3 cells, moderate toxicity to EA.hy926 cells and high toxicity to DU-145 cells. A new avenue towards the treatment of prostate cancer may be opened by the cell-specific cytotoxicity of KNbO3.

The human HOXB13 gene encodes a transcription factor containing a DNA-binding homeobox domain and a HoxA13 N-terminal domain. SNP is considered to be the primary genetic cause for hereditary prostate cancer (PCa). The study of functional nsSNPs would give an insight into the exact cause underlying the onset of hereditary PCa and possible methodologies for the cure or early management of the disease. Several in silico tools were used to screen and map the deleterious nsSNPs to the protein structure for predicting the structure-function effects. Among the 23 homeobox nsSNPs, sift predicted 20, whereas PolyPhen, panther, and provean predicted 21 nsSNP's as deleterious. W63R, D244N, K239Q, P222R, K218R, and G216C were found to have higher energy values than the native 2CRA. The RMSD value showed increased deviation for T253P(2.53 Å), P222R(2.27 Å), G216C(2.15 Å), K218R(1.66 Å), and K239Q(1.62 Å). The I-Mutant showed increase in the stability of R258C, S254T, S250L, K239Q, and Q227E. Ramachandran plot showed mutants P222R, G216C, W263R, and K218R having drastically unfavorable pattern of amino acid residues. The presence of these mutations may result in the altered structure and function of the transcription factor; however, the exact mechanism and pathology of those predicted nsSNPs should further be validated by in vivo experiments and population-based studies., (© 2017 John Wiley & Sons A/S.)

Prostate cancer is one of the most common malignancies among men worldwide. The main aim of the present work was to clarify the advantages of a nanoformulation of ayurvedic herbal plants. Specifically, we assessed the improved anticancer activity of Leucas aspera nanoparticles compared with methanolic crude extract in PC3 prostate cancer cells and normal cells. L. aspera is a plant that is used in ayurveda due to the antirheumatic, antipyretic, anti-inflammatory, antibacterial, anticancer, and cytotoxic activities. Nanoparticles of L. aspera were prepared from plant methanolic extracts. Cytotoxic effect was studied in the normal and prostate cancer cells. Size and morphology of the formulated nanoparticles was assessed using dynamic light scattering and scanning electron microscopy. In vitro cytotoxicity of L. aspera nanoparticles for PC3 cells was concentration- and time-dependent. In vitro hemolysis assay, cellular uptake studies, cell aggregation studies, and cell migration assay established the anticancerous activity of L. aspera in prostate cancer.

The human HOXB13 gene encodes a 284 amino acid transcription factor belonging to the homeobox gene family containing a homeobox and a HoxA13 N-terminal domain. It is highly linked to hereditary prostate cancer, the majority of which is manifested as a result of a Single Nucleotide Polymorphism (SNP). In silico analysis of 95 missense SNP's corresponding to the non-homeobox region of HOXB13 predicted 21 nsSNP's to be potentially deleterious. Among 123 UTR SNPs analysed by UTRScan, rs543028086, rs550968159, rs563065128 were found to affect the UNR_BS, GY-BOX and MBE UTR signals, respectively. Subsequent analysis by PolymiRTS revealed 23 UTR SNPs altering the miRNA binding site. The complete HOXB13_M26 protein structure was modelled using MODELLER v9.17. Computational analysis of the 21 nsSNP's mapped into the HOXB13_M26 protein revealed seven nsSNP's (rs761914407, rs8556, rs138213197, rs772962401, rs778843798, rs770620686 and rs587780165) seriously resulting in a damaging and deleterious effect on the protein. G84E, G135E, and A128V resulted in increased, while, R215C, C66R, Y80C and S122R resulted in decreased protein stability, ultimately predicted to result in the altered binding patterns of HOXB13. While the genotype-phenotype based effects of nsSNP's were assessed, the exact biological and biochemical mechanism driven by the above predicted SNPs still needs to be extensively evaluated by in vivo and GWAS studies.

Background: Flutamide (FLT) is a non steroidal antiandrogenic drug used to treat prostate cancer. Its poor aqueous solubility and toxicity are the major hindrance for oral drug delivery. The aims of this study are to introduce nanoformulation of flutamide to increase its aqueous solubility thereby improves the therapeutic efficacy of the chemodrug., Methods: Poly (vinyl alcohol) (PVA) coated flutamide nanoparticles (PVA FLT NPs) were formulated by nanoprecipitation method and characterized by DLS, TEM, FTIR, Drug release profile and biological assays., Results: The PVA FLT nanoparticles were about 300nm size and spherical in shape. The PVA coated flutamide nanoparticles were monodispersed and polycrystalline. The FTIR spectra confirmed the encapsulation of flutamide in PVA FLT NPs. The encapsulation efficiency and loading efficiency was found to be about 78% and 15% respectively. The in vitro drug release of nanoparticles was calculated and it showed a sustained release up to 120 hrs at pH 7.4. The in vitro cytotoxicity, colony forming ability and blood compatibility were also investigated. The in vitro cytotoxicity study indicated the dose dependent cytotoxicity of PVA FLT NPs. In vitro clonogenic assay revealed that the PVA FLT NPs treated PC3 cells had less colony forming ability than the untreated PC3 cells. In vitro hemolysis assay and blood aggregation studies confirmed the hemocompatibility of the prepared PVA FLT NPs., Conclusion: We reported PVA coated FLT NPs were prepared by nanoprecipitation were more aqueous soluble than FLT, which increased its therapeutic efficacy for prostate cancer cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Recent advances in cancer nanomedicine have attracted remarkable attention in medical sectors. Pharmacologic research on nanomedicines, including targeted cancer therapy, has increased dramatically in the past 5 years. The success stories of nanomedicines in the clinical field include the fabrication of nanomedicines that show maximum loading efficiency into carriers, maximal release kinetics, and minimum toxicity to healthy cells. Nanoparticle-mediated medicines have been developed to specifically target prostate cancer tissue by use of aptamers, antibody targeting, and sustained release of nanomedicines in a dose- and time-dependent manner. Nanomedicines have been developed for therapeutic application in combination with image-guided therapy in real time. The scope of one of these nanomedicines, Abraxane (paclitaxel), may be extended to prostate cancer therapeutic applications for better quality of patient life and longer survival. This review provides an update on the latest directions and developments in nanomedicines for prostate cancer.

Dendritic cell (DC)-based vaccines are considered useful in cancer immunotherapy, and the interaction of DC and adjuvants is important in the design of the next generation vaccines. In this study, whether DC combined with Rv2299c derived from mycobacteria could improve anti-tumor immune responses in a colon cancer mouse model was evaluated. MC38 cell lines were injected subcutaneously to establish colon-cancer-bearing mice and the following four groups were evaluated: PBS control, tumor antigen (TA) loaded-DC, Rv2299c, and a combination of TA-loaded-DC and Rv2299c. The combination treatment with TA-loaded-DC and Rv2299c exhibited greater inhibition of tumor growth compared to other groups. These effects were associated with the reduction of suppressor cells, such as myeloid-derived suppressor cells and regulatory T cells, and the induction of effector cells, such as CD4+ T cells and CD8+ T cells, in spleen, and with the activation of cytotoxic T Lymphocytes and NK cells. These results suggest that TA-loaded-DC vaccination with Rv2299c derived from mycobacteria enhanced anti-tumor immunity in a mouse colon cancer model by inhibiting the generation of immune-suppressive cells and recovering numbers of effector cells, and demonstrated superior polarization of the Th1/Th2 balance in favor of the Th1 immune response.

Prostate cancer has been diagnosed as the second most frequent and the sixth among the cancer causing deaths among men worldwide. There is a limited scope for the prevalent therapies as prostate cancer advances and they present adverse aftermaths that have put way for us to delve into naturally available anticancer agents. The main objective of the present work is to compile the advantages of ayurvedic herbal formulations with modern technology. Baliospermum montanum is a plant that is used in ayurveda for the treatment of cancer and the plant is studied to possess various constituents in it that are responsible for its anticancer activity. Stable nanoparticles of B. montanum were prepared from both the aqueous and ethanolic extracts of the plant and its cytotoxic effects were studied on prostate cancer and normal cell lines. Size analysis by DLS and SEM revealed the average size of nanoparticles prepared was 100±50 nm and 150±50 nm for the nanoparticles prepared from aqueous and ethanolic extract respectively. In vitro cytotoxicity showed a concentration and time dependent toxicity on prostate cancer cells with cell viability of 22% and 6% with maximum concentration of aqueous and ethanolic nanoparticles respectively, in 48 h. In vitro hemolysis assay confirmed that the prepared nanoparticles were compatible with blood with no occurrence of hemolysis. The nanoparticles showed a significant reduction in the colony forming ability and wound healing capacity of the prostate cancer cells. These studies hold the anti cancer potential of the B. montanum nanoparticles making it an important candidate for prostate cancer therapy., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Cancer kinome is now well organized as an important target for a new class of cancer drugs. There are more than 500 members in the kinase family in which some of them are clinically analysed, while the rest are under investigation for potential therapeutic applications. Phosphorylation, major function of kinases is one of the most significant signal transduction mechanism in which intercellular signals regulate intracellular processes like ion transport, hormone responses and cellular proliferation. Any deregulation of kinase function may lead to tumor progression and other disorders such as immunological, neurological , metabolic including also infectious diseases. This led to the necessity in the development of kinase inhibitors as therapeutic agent. Herein we discuss about different types of kinases and their inhibitors in various types of cancers. This review portrays a broad overview of the origin of kinases, discovery, the characterization and mode of action of kinase inhibitors in cancer therapy.

Pancreatic cancer has an infaust prognosis and is the fourth common cause of cancer related death in India. It is highly resistant to conventional treatment modalities such as chemotherapy, radiation therapy and surgery. The association of pancreatic cancer and diabetes mellitus is explored in our study. Pancreatic cancer is more likely to occur in people who have diabetes than people devoid of it, which is supported by the observation that hyperglycaemia occurs at an early stage of pancreatic cancer and is indeed a risk factor. In the present study, we have demonstrated a synergistic relationship between metformin and boswellic acid nanoparticles with varying doses of boswellic acid nanoparticles and constant metformin (20 mM). The effect revealed increased synergism between metformin and boswellic acid nanoparticles through the inhibition of cell proliferation with an effect of 80% for the combination with 0.3 mg/mL and 0.4 mg/mL and a constant concentration of metformin. We examined the effect of combination on cell migration which revealed time dependent inhibitory effect on pancreatic cell line (MiaPaCa-2). Also, we found that the combinatorial approach significantly decreased colony formation and exhibited high rate of induction of apoptosis through DNA fragmentation in pancreatic cancer cells. In-vitro hemolysis confirmed the hemocompatibility of the combination therapy with metformin and boswellic acid nanoparticles. Flow cytometry based apoptosis assay and Caspase mediated apoptosis proved apoptosis mediated cell death. Further, the cells were analysed with mitochondrial membrane potential kit which revealed depolarization of mitochondrial membrane potential due to apoptosis after treatment with drug combination. Hence, the combination approach proved to be a promising therapy towards pancreatic cancer.

Stable nano-formulation of Plumbagin nanoparticles from Plumbago zeylanica root extract was explored as a potential natural drug against prostate cancer. Size and morphology analysis by DLS, SEM and AFM revealed the average size of nanoparticles prepared was 100±50nm. In vitro cytotoxicity showed concentration and time dependent toxicity on prostate cancer cells. However, plumbagin crude extract found to be highly toxic to normal cells when compared to plumbagin nanoformulation, thus confirming nano plumbagin cytocompatibility with normal cells and dose dependent toxicity to prostate cells. In vitro hemolysis assay confirmed the blood biocompatibility of the plumbagin nanoparticles. In wound healing assay, plumbagin nanoparticles provided clues that it might play an important role in the anti-migration of prostate cancer cells. DNA fragmentation revealed that partial apoptosis induction by plumbagin nanoparticles could be expected as a potent anti-cancer effect towards prostate cancer.

Purpose: In vitro anticancer effect and in vivo biodistribution and biocompatibility of metformin encapsulated O-Carboxymethyl chitosan nanoparticles were evaluated for its application as pancreatic cancer therapy., Methods: In vitro studies such as cell migration assay, clonogenic assay, cell cycle analysis and qRT-PCR analysis were done in pancreatic cancer cells (MiaPaCa-2) treated with O-CMC-metformin NPs for evaluating its anticancer potential. In vivo biodistribution studies were carried out by NIR imaging of O-CMC-metformin NPs after tagging it with ICG. In vivo biocompatibility of the NPs was assessed by histopathology analysis of organs from mice administered with the NPs., Results: In vitro cell migration assay showed marginal effect of NPs on migration property of pancreatic cancer cells (MiaPaCa-2). In vitro clonogenic assay established that the O-CMC-metformin NPs reduced colony formation ability of the cancer cells. While cell cycle analysis showed that the O-CMC-metformin NPs had only minor effect on progression of cell cycle in the cancer cells. qRT-PCR analysis exhibited reduced mRNA expression of p21, vanin 1 and MMP9 in pancreatic cancer cells treated with the nanoparticles. In vivo NIR imaging study showed normal biodistribution pattern of the intravenously injected O-CMC-metformin NPs suggesting normal clearance rate of nanoparticles and no adverse toxicity to the organs., Conclusions: The biocompatible O-CMC-metformin NPs with anticancer potential and capability for normal biodistribution can be beneficial for the treatment of pancreatic cancer.

Background: Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model., Methods: CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC., Results: The 5-FU-TCS-NPs (size: 150±40nm, zeta potential: +48.2±5mV) and CRC-TCS-NPs (size: 150±20nm, zeta potential: +35.7±3mV) were proven to be compatible with blood. The in vitro drug release studies at pH4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72h, unlike bare CRC and 5-FU., Conclusions: To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo., General Significance: The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Colon cancer is the third most leading causes of death due to cancer worldwide and the chemo drug 5-fluorouracil's (5-FU) applicability is limited due to its non-specificity, low bioavailability and overdose. The efficacy of 5-FU in colon cancer chemo treatment could be improved by nanoencapsulation and combinatorial approach. In the present study curcumin (CUR), a known anticancer phytochemical, was used in combination with 5-FU and the work focuses on the development of a combinatorial nanomedicine based on 5-FU and CUR in N,O-carboxymethyl chitosan nanoparticles (N,O-CMC NPs). The developed 5-FU-N,O-CMC NPs and CUR-N,O-CMC NPs were found to be blood compatible. The in vitro drug release profile in pH 4.5 and 7.4 showed a sustained release profile over a period of 4 days. The combined exposure of the nanoformulations in colon cancer cells (HT 29) proved the enhanced anticancer effects. In addition, the in vivo pharmacokinetic data in mouse model revealed the improved plasma concentrations of 5-FU and CUR which prolonged up to 72 h unlike the bare drugs. In conclusion, the 5-FU and CUR released from the N,O-CMC NPs produced enhanced anticancer effects in vitro and improved plasma concentrations under in vivo conditions., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Lung cancer, associated with the up-regulated epidermal growth factor receptor (EGFR) led to the development of EGFR targeted anticancer therapeutics. The biopolymeric nanoparticles form an outstanding system for the targeted delivery of therapeutic agents. The present work evaluated the in vitro effects of chitosan cross-linked γ-poly(glutamic acid) (γ-PGA) nanoparticles (Nps) loaded with docetaxel (DTXL) and decorated with Cetuximab (CET), targeted to EGFR over-expressing non-small-cell-lung-cancer (NSCLC) cells (A549). CET-DTXL-γ-PGA Nps was prepared by ionic gelation and CET conjugation via EDC/NHS chemistry. EGFR specificity of targeted Nps was confirmed by the higher uptake rates of EGFR +ve A549 cells compared to that of EGFR -ve cells (NIH3T3). The cytotoxicity of Nps quantified using cell based (MTT/LDH) and flowcytometry (Cell-cycle analysis, Annexin V/PI and JC-1) assays showed superior antiproliferative activity of CET-DTXL-γ-PGA Nps over DTXL-γ-PGA Nps. The A549 cells treated with CET-DTXL-γ-PGA NPs underwent a G2/M phase cell cycle arrest followed by reduction in mitochondrial membrane potential of A549 cells, inducing apoptosis and necrosis resulting in enhanced cancer cell death. CET-DTXL-γ-PGA Nps exhibited enhanced cellular internalization and therapeutic activity, by actively targeting EGFR on NSCLC cells and hence could be an effective alternative to non-specific, conventional chemotherapy by increasing its efficiency by many folds., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Receptor targeted therapy is advantageous in overcoming the toxicity burden of conventional cancer chemotherapeutics. Over expression of epidermal growth factor receptor (EGFR) on cancer cells and its role in metastasis, malignancy and drug resistance in many human cancers lead to its selection as a promising target for cancer treatment. The present work investigated the preparation and characterization of docetaxel (DTXL) loaded gamma-poly (glutamic acid) (gamma-PGA) nanoparticles (Nps) conjugated with EGFR antibody (Cetuximab, CET) targeted to colon cancer cells (HT-29), highly over expressing EGFR. The flow cytometric analysis revealed two fold increased cellular uptake of CET-DTXL-gamma-PGA Nps by HT-29 (EGFR +ve) cells compared to that of IEC-6 (EGFR-ve) cells confirming the active targeting. Cytotoxicity assays (MTT and LDH) showed superior anti-proliferative activity of CET-DTXL-gamma-PGA NPs over DTXL-gamma-PGA Nps against HT-29 cells. The cell cycle analysis indicated that CET-DTXL-gamma-PGA NPs induced cell death in enhanced percentage of HT-29 cells by undergoing cell cycle arrest in G2/M phase compared to that of DTXL-gamma-PGA Nps. The mechanism of cancer cell death was analyzed via apoptotic and mitochondrial membrane potential assays and showed that targeted Nps treatment reduced the mitochondrial membrane potential thereby inducing enhanced HT-29 cell death (apoptosis and necrosis). The biodistribution of targeted and non-targeted Nps were analyzed in vivo in Swiss albino mice using NIR imaging. ICG-CET-DTXL-gamma-PGA Nps (targeted) and ICG-DTXL-gamma-PGA Nps (non-targeted) followed the similar biodistribution pattern in vivo, but with different elimination time. In short, CET-DTXL-gamma-PGA nanoparticles enhance the tumor selective therapeutic efficacy for colon cancer.

Silymarin, a clinically proved hepato-protective herbal drug having significant anti-cancerous property towards prostate cancer, is inadequately utilized for cancer therapy due to its hydrophobic nature and poor bioavailability. In this work, we have developed silymarin Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in order to improve the therapeutic efficacy of silymarin towards prostate cancer by single emulsion solvent evaporation technique. The prepared nanoparticles had an encapsulation efficiency of 60% and a loading efficiency of 13%. The silymarin-PLGA NPs (SNPs) characterization, using DLS and SEM analysis revealed its size as less than 300 nm. FT-IR analysis confirmed encapsulation of silymarin by the SNPs, whereas XRD and TGA proved amorphous nature of the SNPs. In vitro drug release study demonstrated a slow and sustained release of encapsulated drug from the SNPs in physiological conditions. The hemocompatibility of the SNPs was established by in vitro hemolysis and coagulation assays. In vitro cell viability studies revealed preferential toxicity of SNPs towards prostate cancer cells (PC-3) compared to normal cells (Vero) in a dose dependant way. Cell uptake studies using confocal microscopy confirmed internalization of the SNPs by PC-3 cells. Furthermore, in vitro cell migration assay showed a concentration and time dependent inhibitory effect of SNPs on PC-3 cell migration. Finally, flow-cytometry based apoptosis assay suggested induction of apoptosis mediated death in PC-3 cells by the SNPs. Overall, the prepared SNPs proved as a promising candidate for prostate cancer therapy.

Metformin, a biguanide, is a commonly administered drug for the management of type 2 diabetes mellitus. The drug received tremendous recognition, when retrospective studies proved metformin-associated reduction in cancer risk. Metformin has potential anticancer effects and an ability to suppress tumor growth both in vitro and in vivo. Activation of LKB1/AMPK pathway and cancer stem cell destruction along with cell cycle arrest and apoptosis induction are the proposed mechanisms of anticancer potential of metformin. Nanotechnology approaches have also been adopted for metformin delivery to cancer cells. This review directs on the application of metformin for the therapy of various cancers and also the different pathways responsible for the metformin derived anticancer effect. It also focuses on the pharmacological applications of metformin and the nanotechnology approaches for metformin delivery.

Recent advancements in cancer nanotechnology have facilitated a better way to diagnosis and provide therapy for prostate cancer. Nanotechnology has the potential to battle tumors at the site, where the cancer begins. There is a need to improve the therapeutic availabilities and the effectiveness of conventional chemotherapeutic agents for prostate cancer. Many therapeutic NPs have been developed with nanotechnology that can specifically target and deliver variety of agents including chemo drugs to destruct the prostate cancer cells without causing any damage to the healthy cells. Theranostic NPs have been developed to specifically target the prostate cancer cells using targeting ligands and to release the anticancer agents in a controlled and time-dependent manner for cancer therapy in combination with assisted imaging to monitor the effectiveness of the therapy in real time. The natural products and surface-modified polymers and metallic NPs have evolved as promising nanomaterials for targeted prostate cancer treatment. This review focuses on the role of alternative medicine, polymeric and metallic and metal oxide NPs in prostate cancer theranostics.

In this work, we have developed a nanocomposite scaffold using a mixture of pectin, chitin and nano CaCO3 using the technique of lyophilization, with an intended use towards biomedical applications such as tissue engineering and drug delivery. The prepared composite scaffold was characterized using scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). In addition, swelling, degradation and biomineralization capability of the composite scaffold was evaluated. The developed composite scaffold showed controlled swelling and degradation in comparison with the control scaffold. Cytocompatibility evaluation of the scaffold was tested on NIH3T3, L929 and human dermal fibroblast (HDF) cells, showed negligible toxicity towards cells. Cell attachment and proliferation studies were also conducted using these cells, which showed that cells attached onto the scaffolds and started to proliferate after 48 h of incubation. Further, drug delivery through the scaffold was examined using a bisphosphonate called Fosamax. These results suggest that the developed composite scaffold possess the essential requisites for their application in the fields of tissue engineering and drug delivery., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Ovarian cancer is the ninth most common cancer amongst women and ranked as fifth in terms of the cause of cancer related mortality accounting for more deaths than any other cancer of the female reproductive system. Gemcitabine is the most common chemotherapeutic agent used in the treatment of ovarian cancer despite of its disadvantage of having a very lesser half life. In this study, we have envisaged the use of a highly porous, biomimetic and implantable pectin scaffold embedded with gemcitabine loaded fibrin nanoconstructs to improve the half life of the drug, thereby providing localized therapy for ovarian cancer. The controlled and sustained release of the chemokine from the scaffold system was extensively analyzed in vitro different pH environments. The composite scaffolds were found to be highly biocompatible when tested with mammalian cell lines. The excellent cytotoxicity and apoptosis responses induced in ovarian cancer, PA- 1 cell lines proved that the nanocomposite Pectin scaffolds loaded with specific chemokine can be used as implantable "therapeutic wafers" for distracting metastatic cancer cells and thus improve the survival rate of ovarian cancer afflicted individuals.

In the current work, a sustained drug delivery system of flutamide (FLT) was developed using chitosan (CS) and dextran sulphate (DS) nanoparticles and were characterized using different techniques. The prepared nanoparticles showed a size of 80-120 nm with an entrapment efficiency of 55 +/- 6.95%. In addition, blood compatibility, in vitro cytotoxicity, drug release and cellular uptake studies were also carried out. The drug release studies showed a sustained and pH dependent release pattern as a result, after 120 h about 66% drug release occurred at pH 7.4 and 78% release occurred in acidic pH. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) experiments proved the preferential toxicity of drug loaded nanoparticles towards prostate cancer cells (PC3) unlike in normal cells, mouse fibroblast cells (L929). The cell death mechanism of drug loaded nanoparticles for a concentration of 50 and 75 nM showed 28 +/- 2 and 35.2 +/- 4% apoptosis in samples treated with the PC3 cells after 24 h. Fluorescent microscopic imaging and flow cytometry confirmed the preferential uptake of the nanoparticles (NPs) in the prostate cancer cells (PC3) unlike in normal (L929) cells. Hence the developed FLT loaded CS-DS NPs could be used as a promising system for controlled delivery in prostate cancer.

In this work, Hemigraphis alternata extract incorporated chitosan scaffold was synthesized and characterized for wound healing. The antibacterial activity of Hemigraphis incorporated chitosan scaffold (HIC) against Escherichia coli and Staphylococcus aureus was evaluated which showed a reduction in total colony forming units by 45-folds toward E. coli and 25-fold against S. aureus respectively. Cell viability studies using Human Dermal Fibroblast cells (HDF) showed 90% viability even at 48 h when compared to the chitosan control. The herbal scaffold made from chitosan was highly haemostatic and antibacterial. The obtained results were in support that the herbal scaffold can be effectively applied for infectious wounds., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: β-chitin hydrogel/nZnO composite bandage was fabricated and evaluated in detail as an alternative to existing bandages., Methods: β-chitin hydrogel was synthesized by dissolving β-chitin powder in Methanol/CaCl(2) solvent, followed by the addition of distilled water. ZnO nanoparticles were added to the β-chitin hydrogel and stirred for homogenized distribution. The resultant slurry was frozen at 0°C for 12 h. The frozen samples were lyophilized for 24 h to obtain porous composite bandages., Results: The bandages showed controlled swelling and degradation. The composite bandages showed blood clotting ability as well as platelet activation, which was higher when compared to the control. The antibacterial activity of the bandages were proven against Staphylococcus aureus (S. aureus) and Escherichia coli (E.coli). Cytocompatibility of the composite bandages were assessed using human dermal fibroblast cells (HDF) and these cells on the composite bandages were viable similar to the Kaltostat control bandages and bare β-chitin hydrogel based bandages. The viability was reduced to 50-60% in bandages with higher concentration of zinc oxide nanoparticles (nZnO) and showed 80-90% viability with lower concentration of nZnO. In vivo evaluation in Sprague Dawley rats (S.D. rats) showed faster healing and higher collagen deposition ability of composite bandages when compared to the control., Conclusions: The prepared bandages can be used on various types of infected wounds with large volume of exudates.

This study focuses on development and evaluation of 5-fluorouracil (5-FU) loaded chitin nanogels (FCNGs). It formed good, stable aqueous dispersion with spherical particles in 120-140 nm size range and showed pH responsive swelling and drug release. The FCNGs showed toxicity on melanoma (A375) in a concentration range of 0.4-2.0mg/mL, but less toxicity toward human dermal fibroblast (HDF) cells by MTT assay. Confocal analysis revealed uptake of FCNGs by both cells. From skin permeation experiments, FCNGs showed almost same steady state flux as that of control 5-FU but the retention in the deeper layers of skin was found to be 4-5 times more from FCNGs. Histopathological evaluation revealed loosening of the horny layer of epidermis by interaction of cationically charged chitin, with no observed signs of inflammation and so FCNGs can be a good option for treatment of skin cancers., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We developed chitin hydrogel/nano ZnO composite bandages using chitin hydrogel and ZnO nanoparticles (nZnO). The homogenized mixture of chitin hydrogel and nZnO was freeze-dried to obtain micro-porous composite bandages. The prepared nanocomposite bandages were characterized using FT-IR, XRD and SEM. In addition, blood clotting, antibacterial, swelling, cytocompatibility and cell attachment capability of the prepared nanocomposite bandages were evaluated. The nanocomposite bandages showed enhanced swelling, blood clotting and antibacterial activity. The incorporation of nZnO helped to attain antibacterial activity. Cytocompatibility studies were carried out using human dermal fibroblast (HDF) cells proved the non-toxic nature of the composite bandages. HDF cell attachment and infiltration analysis showed that the cells were attached and penetrated into the interior (250 microm) of the nanocomposite bandages. These studies revealed that, this nanocomposite can be used for burn, diabetic and chronic wound defects.

In this work we developed metformin loaded O-carboxymethyl chitosan (O-CMC) nanoparticles (NPs) by ionic-gelation method. The prepared NPs of 240 ± 50 nm size with spherical morphology exhibited a pH sensitive release of metformin in vitro. Cytotoxicity studies showed that the drug-incorporated NPs induced significant toxicity on pancreatic cancer cells (MiaPaCa-2) compared to normal cells (L929). Metformin loaded NPs exhibited nonspecific internalization by normal and pancreatic cancer cells; however metformin released from the NPs induced preferential toxicity on pancreatic cancer cells. Our preliminary studies suggested that such a novel approach could possibly overcome the current limitations of metformin in its clinical application against pancreatic cancer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Current wound dressings have disadvantages such as less flexibility, poor mechanical strength, lack of porosity, and a tendency for dressings to adhere onto the wound surface; in addition, a majority of the dressings did not possess antibacterial activity. Hydrogel-based wound dressings would be helpful to provide a cooling sensation and a moisture environment, as well as act as a barrier to microbes. To overcome these hassles, we have developed flexible and microporous chitosan hydrogel/nano zinc oxide composite bandages (CZBs) via the incorporation of zinc oxide nanoparticles (nZnO) into chitosan hydrogel. The prepared nanocomposite bandages were characterized using Fourier transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), and scanning electron microscopy (SEM). In addition, swelling, degradation, blood clotting, antibacterial, cytocompatibility, cell attachment on the material, and cell infiltration into the composite bandages were evaluated. The nanocomposite bandage showed enhanced swelling, blood clotting, and antibacterial activity. Cytocompatibility of the composite bandage has been analyzed in normal human dermal fibroblast cells. Cell attachment and infiltration studies showed that the cells were found attached to the nanocomposite bandages and penetrated into the interior. Furthermore, the in vivo evaluations in Sprague-Dawley rats revealed that these nanocomposite bandages enhanced the wound healing and helped for faster re-epithelialization and collagen deposition. The obtained data strongly encourage the use of these composite bandages for burn wounds, chronic wounds, and diabetic foot ulcers.

In this study, curcumin loaded chitin nanogels (CCNGs) were developed using biocompatible and biodegradable chitin with an anticancer curcumin drug. Chitin, as well as curcumin, is insoluble in water. However, the developed CCNGs form a very good and stable dispersion in water. The CCNGs were analyzed by DLS, SEM and FTIR and showed spherical particles in a size range of 70-80 nm. The CCNGs showed higher release at acidic pH compared to neutral pH. The cytotoxicity of the nanogels were analyzed on human dermal fibroblast cells (HDF) and A375 (human melanoma) cell lines and the results show that CCNGs have specific toxicity on melanoma in a concentration range of 0.1-1.0 mg mL(-1), but less toxicity towards HDF cells. The confocal analysis confirmed the uptake of CCNGs by A375. The apoptotic effect of CCNGs was analyzed by a flow-cytometric assay and the results indicate that CCNGs at the higher concentration of the cytotoxic range showed comparable apoptosis as the control curcumin, in which there was negligible apoptosis induced by the control chitin nanogels. The CCNGs showed a 4-fold increase in steady state transdermal flux of curcumin as compared to that of control curcumin solution. The histopathology studies of the porcine skin samples treated with the prepared materials showed loosening of the horny layer of the epidermis, facilitating penetration with no observed signs of inflammation. These results suggest that the formulated CCNGs offer specific advantage for the treatment of melanoma, the most common and serious type of skin cancer, by effective transdermal penetration.

α-chitin hydrogel/nano hydroxyapatite (nHAp) composite scaffold have been synthesized by freeze-drying approach with nHAp and α-chitin hydrogel. The prepared nHAp and nanocomposite scaffolds were characterized using DLS, SEM, FT-IR, XRD and TGA studies. The porosity, swelling, degradation, protein adsorption and biomineralization (calcification) of the prepared nanocomposite scaffolds were evaluated. Cell viability, attachment and proliferation were investigated using MG 63, Vero, NIH 3T3 and nHDF cells to confirm that the nanocomposite scaffolds were cytocompatible and cells were found to attach and spread on the scaffolds. All the results suggested that these scaffolds can be used for bone and wound tissue engineering., (Copyright © 2011 Elsevier B.V. All rights reserved.)