Curcumin-loaded nanoparticles effectively prevent T4-induced oxidative stress in rat heart.

In this study, we report the cardioprotective effect of the glycerol monooleate (GMO) based nanocurcumin in both in vitro and in vivo conditions under a hyperthyroid state. The heart is one of the primary target organs sensitive to the action of thyroid hormone, and slight variations in the thyroid hormone serum concentrations result in measurable changes in cardiac performance. Hyperthyroidism-induced hypermetabolism is associated with oxidative stress and is an important mechanism responsible for the progression of heart failure. Curcumin has been known to play a protective role against oxidative stress-related diseases like Alzheimer's, asthma, and aging due to its antioxidant properties. Nevertheless, its potent biological activity has been hindered due to its poor bioavailability. To overcome this drawback, a GMO-based biodegradable nanoparticle (NP) formulation loaded with curcumin has been developed, and the protective effect of curcumin-loaded NPs was compared against the native drug. Oxidative stress parameters like reactive oxygen species (ROS) release, change in mitochondrial membrane permeability, lipid peroxidation (LPx), lactate dehydrogenase (LDH) release, and the activity and protein expression of the endogenous antioxidant enzymes like superoxide dismutase, catalase (CAT) and glutathione peroxidase were evaluated. The results from in vitro showed that curcumin-loaded NPs showed better DPPH and NO radical scavenging activity than native curcumin in a concentrations range of 2.5-20 µM. It was also observed that the nanoparticulate curcumin was comparatively more effective than native curcumin in protecting against ROS-induced membrane damage by reducing LPx and LDH leakage at low concentrations of 5-10 µM. Further, curcumin NPs performed better in facilitating the activities of antioxidant enzymes under in vitro and in vivo conditions with respect to time and concentrations, resulting in reduced cellular ROS levels. In this scenario, we anticipate that curcumin-loaded NPs can serve as a better antioxidant than its native counterpart in protecting the heart from oxidative stress-related diseases.

Smart Cancer Nanomedicine for Synergetic Therapy.

Cancer is the second leading cause of death. Notwithstanding endeavors to comprehend tumor causes and therapeutic modalities, no noteworthy advancements in cancer therapy have been identified. Nanomedicine has drawn interest for its diagnostic potential because of its ability to deliver therapeutic agents specifically to tumors with little adverse effects. Nanomedicines have become prevalent in the treatment of cancer. Here, we present four strategic suggestions for improvement in the functionality and use of nanomedicine. (1) Smart drug selection is a prerequisite for both medicinal and commercial achievement. Allocating resources to the advancement of modular (pro)drugs and nanocarrier design ought to consider the role of opportunistic decisions depending on drug availability. (2) Stimuli-responsive nanomedicine for cancer therapy is being designed to release medications at particular locations precisely. (3) The cornerstone of clinical cancer treatment is combination therapy. Nanomedicines should be included more frequently in multimodal combination therapy regimens since they complement pharmacological and physical co-treatments. (4) Regulation by the immune system is transforming cancer therapy. Nanomedicines can improve the effectiveness of the immune system and control the behavior of anticancer immunity. These four approaches, both separately and particularly in combination, will accelerate and promote the creation of effective cancer nanomedicine treatments.

In silico screening of phytoconstituents as potential anti-inflammatory agents targeting NF-κB p65: an approach to promote burn wound healing.

Chronic burn wounds are frequently characterised by a prolonged and dysregulated inflammatory phase that is mediated by over-activation of NF-κB p65. Synthetic wound healing drugs used for treatment of inflammation are primarily associated with several shortcomings which reduce their therapeutic index. In this scenario, phytoconstituents that exhibit multifaceted biological activities including anti-inflammatory effects have emerged as a promising therapeutic alternative. However, identification and isolation of phytoconstituents from medicinal herbs is a cumbersome method that is linked to profound uncertainty. Hence, present study aimed to identify prospective phytoconstituents as inhibitors of RHD of NF-κB p65 by utilizing in silico approach. Virtual screening of 2821 phytoconstituents was performed against protein model. Out of 2821 phytoconstituents, 162 phytoconstituents displayed a higher binding affinity (≤ -8.0 kcal/mol). These 162 phytoconstituents were subjected to ADMET predictions, and 15 of them were found to satisfy Lipinski's rule of five and showed favorable pharmacokinetic properties. Among these 15 phytoconstituents, 5 phytoconstituents with high docking scores i.e. silibinin, bismurrayaquinone A, withafastuosin B, yuccagenin, (+)-catechin 3-gallate were selected for molecular dynamics (MD) simulation analysis. Results of MD simulation indicated that withafastuosin B, (+)-catechin 3-gallate and yuccagenin produced a compact and stable complex with protein without significant variations in conformation. Relative binding energy analysis of best hit molecules indicate that withafastuosin B, and (+)-catechin 3-gallate exhibit high binding affinity with target protein among other lead molecules. Findings of study suggest that these phytoconstituents could serve as promising anti-inflammatory agents for treatment of burn wounds by inhibiting the RHD of NF-κB p65.Communicated by Ramaswamy H. Sarma.

A novel in vitro three-dimensional retinoblastoma model for evaluating chemotherapeutic drugs.

PURPOSE: Novel strategies are being applied for creating better in vitro models that simulate in vivo conditions for testing the efficacy of anticancer drugs. In the present study we developed surface-engineered, large and porous, biodegradable, polymeric microparticles as a scaffold for three dimensional (3-D) growth of a Y79 retinoblastoma (RB) cell line. We evaluated the effect of three anticancer drugs in naïve and nanoparticle-loaded forms on a 3-D versus a two-dimensional (2-D) model. We also studied the influence of microparticles on extracellular matrix (ECM) synthesis and whole genome miRNA-gene expression profiling to identify 3D-responsive genes that are implicated in oncogenesis in RB cells. METHODS: Poly(D,L)-lactide-co-glycolide (PLGA) microparticles were prepared by the solvent evaporation method. RB cell line Y79 was grown alone or with PLGA-gelatin microparticles. Antiproliferative activity, drug diffusion, and cellular uptake were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole (MTT) assay, fluorescent microscope, and flow cytometry. Extra cellular matrix (ECM) synthesis was observed by collagenase assay and whole genome miRNA-microarray profiling by using an Agilent chip. RESULTS: With optimized composition of microparticles and cell culture conditions, an eightfold increase from the seeding density was achieved in 5 days of culture. The antiproliferative effect of the drugs in the 3-D model was significantly lower than in the 2-D suspension, which was evident from the 4.5 to 21.8 fold differences in their IC(50) values. Using doxorubicin, the flow cytometry data demonstrated a 4.4 fold lower drug accumulation in the cells grown in the 3-D model at 4 h. The collagen content of the cells grown in the 3-D model was 2.3 fold greater than that of the cells grown in the 2-D model, suggesting greater synthesis of the extracellular matrix in the 3-D model as the extracellular matrix acted as a barrier to drug diffusion. The microarray and miRNA analysis showed changes in several genes and miRNA expression in cells grown in the 3-D model, which could also influence the environment and drug effects. CONCLUSIONS: Our 3-D retinoblastoma model could be used in developing effective drugs based on a better understanding of the role of chemical, biologic, and physical parameters in the process of drug diffusion through the tumor mass, drug retention, and therapeutic outcome.

Sustained wound healing activity of curcumin loaded oleic acid based polymeric bandage in a rat model.

Wound healing is an intricate multistage process that includes inflammation, cell proliferation, matrix deposition and remodeling phases. It is often associated with oxidative stress and consequent prolonged inflammation, resulting in impaired wound healing. Curcumin has been reported to improve wound healing in different animal models. In order to increase the efficacy of curcumin in the healing arena a curcumin loaded oleic acid based polymeric (COP) bandage was formulated. The in vivo wound healing potency was compared with void bandage and control (cotton gauze treatment) in a rat model. Biochemical parameters and histological analysis revealed increased wound reduction and enhanced cell proliferation in COP bandage treated groups due to its efficient free radical scavenging properties. Comparative acceleration in wound healing was due to early implementation of fibroblasts and its differentiation (increased level of α-smooth muscle actin). Western blotting and semiquantitative PCR analysis clearly indicate that COP bandage can efficiently quench free radicals leading to reduced antioxidative enzyme activity. Further evidence at mRNA and protein level indicates that our system is potent enough to reduce the inflammatory response mediated by the NFκB pathway during wound healing. With this background, we anticipate that such a versatile approach may seed new arena for topical wound healing in the near future.

Computational study to evaluate the potency of phytochemicals in Boerhavia diffusa and the impact of point mutation on cyclin-dependent kinase 2-associated protein 1.

A protein's function is closely related to its structural properties. Mutations can affect the functionality of a protein. Different cancer tissues have found disordered expression of the cyclin-dependent kinase 2-associated Protein 1 (CDK2AP1) gene. A protein molecule's conformational flexibility affects its interaction with phytochemicals and their biological partners at various levels. Boerhavia diffusa has been investigated most extensively for its medicinal activities like anticancer properties. It contains many bioactive compounds like Boeravinone A, Boeravinone B, Boeravinone C, Boeravinone D, Boeravinone E, Boeravinone F, Boeravinone G, Boeravinone H, Boeravinone I and Boeravinone J. We have studied to analyse the binding efficacy properties as well as essential dynamic behaviour, free energy landscape of both the native and mutant protein CDK2AP1 with bioactive compounds from Boerhavia diffusa plant extracts through computational approaches by homology modelling, docking and molecular dynamics simulation. From the molecular docking study, we found that. Boeravinone J have best binding affinity (-7.9 kcal/mol) towards the native protein of CDKAP1 compared to others phytochemicals. However, we found the binding energy for H23R and C105R (mutation point) -7.8 and -7.6 kcal/mol, respectively. A single minima energy point (from 100 ns molecular dynamics simulation study) was found in the H23R mutant with Boeravinone J complex suggested that minimum structural changes with less conformational mobility compared C105A mutant model.Communicated by Ramaswamy H. Sarma.

The prospective of Artificial Intelligence in COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) is a major threat throughout the world. The latest advancements in the field of computational techniques based on Artificial Intelligence (AI), Machine Learning (ML) and Big Data can help in detecting, monitoring and forecasting the severity of the COVID-19 pandemic. We aim to review the detection of the COVID-19 pandemic empowered by AI, major implications, challenges and the future of smart health care at a glance. The AI plays a pioneering role in rapid and improved detection of the disease. It helps in modeling the disease activity and predicting the severity for better decision making and preparedness by healthcare authorities and policymakers. It is a promising technology for automatic and fully transparent monitoring system to track and treat the patients remotely without spreading the virus to others. The future application areas of AI-based healthcare are also identified. The role of AI in tackling the COVID-19 pandemic is reviewed in this paper. AI proves beneficial in early detection with improved results. It also provides solution for contact tracing, prediction, drug development thus reducing the workload of medical industry.

Modern computational intelligence based drug repurposing for diabetes epidemic.

BACKGROUND AND AIM: Objectives are to explore recent advances in discovery of new antidiabetic agents using repurposing strategies and to discuss modern technologies used for drug repurposing highlighting diabetic specific web portal. METHODS: Recent literature were studied and analyzed from various sources such as Scopus, PubMed, and IEEE Xplore databases. RESULTS: Drugs like Niclosamideethanolamine, Methazolamide, Diacerein, Berberine, Clobetasol, etc. with possibility of repurposing to curb diabetes can be potential late-stage clinical candidates, providing access to information on pharmacology, formulation, and probable toxicity if any. CONCLUSIONS: With collaboration of artificial intelligence (AI) with pharmacology, the efficiency of drug repurposing can improve significantly.

A human epidermal growth factor-curcumin bandage bioconjugate loaded with mesenchymal stem cell for in vivo diabetic wound healing.

Bone-marrow-derived mesenchymal stem cells (MSCs) are of growing interest for the treatment of diabetic wound healing. However, they are often associated with poor proliferation and viability at the wounded site. Here, it is reported the use of human epidermal growth factor -curcumin bandage bioconjugate (EGF-Cur B) loaded with MSCs (MSCs-EGF-Cur B) at the wounded site for diabetic wound healing. Conjugation efficiency of EGF was determined by FTIR and XPS, surface morphology was analyzed by SEM and AFM and hydrophilicity by contact angle. Chemical integrity of curcumin with the polymeric matrix was studied by FTIR and, antiinflamatory and biocompatibility of EGF-Cur B were determined by TNF α ELISA and MTT study respectively. The culture of MSCs over EGF-Cur B enhanced MSC viability and expression of transcription factors associated with the maintenance of pluripotency and self-renewal (OCT¾, SOX2, and Nanog) as compared to MSCs grown in standard conditions. Its therapeutic effect was examined on diabetic full-thickness excisional wound model in terms of size and histological examination. Synergetic combinational approach especially when treated with MSCs-EGF-Cur B significantly enhanced wound closure by increasing granulation tissue formation, collagen deposition, and angiogenesis as compared to other groups. In conclusion, biocompatible therapeutic MSCs-EGF-Cur B might have great application for diabetic wound healing in the near future.

Application of cognitive Internet of Medical Things for COVID-19 pandemic.

BACKGROUND AND AIM: In the age of advanced digital technology, smart healthcare based on the Internet of Things (IoT) is gaining importance to deal with the current COVID-19 pandemic. In this paper, the novel application of cognitive radio (CR) based IoT specific for the medical domain referred to as Cognitive Internet of Medical Things (CIoMT) is explored to tackle the global challenge. This concept of CIoT is best suited to this pandemic as every person is to be connected and monitored through a massive network that requires efficient spectrum management. METHODS: An extensive literature survey is conducted in the Google Scholar, Scopus, PubMed, Research Gate, and IEEE Xplore databases using the terms "COVID-19" and "Cognitive IoT" or "Corona virus" and "IoMT". The latest data and inputs from official websites and reports are used for further investigation and analysis of the application areas. RESULTS: This review encompasses different novel applications of CIoMT for fighting the ongoing COVID-19 health crisis. The CR based dynamic spectrum allocation technique is the solution for accommodating a massive number of devices and a wide number of applications. The CIoMT platform enables real-time tracking, remote health monitoring, rapid diagnosis of the cases, contact tracking, clustering, screening, and surveillance thus, reducing the workload on the medical industry for prevention and control of the infection. The challenges and future research directions are also identified. CONCLUSIONS: CIoMT is a promising technology for rapid diagnosis, dynamic monitoring and tracking, better treatment and control without spreading the virus to others.

Application of Artificial Intelligence in COVID-19 drug repurposing.

BACKGROUND AND AIM: COVID-19 outbreak has created havoc and a quick cure for the disease will be a therapeutic medicine that has usage history in patients to resolve the current pandemic. With technological advancements in Artificial Intelligence (AI) coupled with increased computational power, the AI-empowered drug repurposing can prove beneficial in the COVID-19 scenario. METHODS: The recent literature is studied and analyzed from various sources such as Scopus, Google Scholar, PubMed, and IEEE Xplore databases. The search terms used are 'COVID-19', ' AI ', and 'Drug Repurposing'. RESULTS: AI is implemented in the field design through the generation of the learning-prediction model and performs a quick virtual screening to accurately display the output. With a drug-repositioning strategy, AI can quickly detect drugs that can fight against emerging diseases such as COVID-19. This technology has the potential to improve the drug discovery, planning, treatment, and reported outcomes of the COVID-19 patient, being an evidence-based medical tool. CONCLUSIONS: Thus, there are chances that the application of the AI approach in drug discovery is feasible. With prior usage experiences in patients, few of the old drugs, if shown active against SARS-CoV-2, can be readily applied to treat the COVID-19 patients. With the collaboration of AI with pharmacology, the efficiency of drug repurposing can improve significantly.

Protective efficacy of crocetin and its nanoformulation against cyclosporine A-mediated toxicity in human embryonic kidney cells.

AIM: This study is aimed to formulate crocetin-loaded lipid Nanoparticles (NPs) and to evaluate its antioxidant properties in a cyclosporine A-mediated toxicity in Human Embryonic Kidney (HEK-293) cells in vitro. MAIN METHODS: Crocetin-loaded NPs were prepared followed by physicochemical characterization. In vitro protective efficacy of crocetin and crocetin loaded NPs was investigated in cyclosporine A-mediated toxicity in HEK-293 cells by assessing free radical scavenging, DNA Nicking, cytotoxicity, intracellular Reactive oxygen species (ROS) inhibition, Mitochondrial membrane potential (MMPs) loss and evaluating the activity and expression of antioxidant enzymes and non-enzyme level. Further, we have studied the mechanism of protective activity of crocetin either native or in NPs by studying the expression of phase II detoxifying proteins (HO-1) via Nrf2 mediated regulation. KEY FINDINGS: Our results showed that pretreatment with crocetin and crocetin-loaded NPs attenuated the cyclosporine A-mediated toxicity, ROS production and exhibited enhance free radical scavenging ability and cytoprotective activity. Further, the treatment prevented MMPs loss by directly scavenging the ROS and restored the antioxidant enzyme network with normalization of heme oxygenase-1 (HO-1) expression by inhibiting nuclear translocation of Nrf2. SIGNIFICANCE: Pretreatment of crocetin and crocetin-loaded NPs provided pronounce protective effect against cyclosporine A-mediated toxicity in HEK-293 cells by nullifying the ROS formation and restored antioxidant network through inhibition of Nrf2 translocation and followed by expression of HO-1. Such an approach may be anticipated to be beneficial for antioxidant therapy.

Curcumin and its topical formulations for wound healing applications.

Oxidative damage and inflammation have been identified, through clinical and preclinical studies, as the main causes of nonhealing chronic wounds. Reduction of persistent chronic inflammation by application of antioxidant and anti-inflammatory agents such as curcumin has been well studied. However, low aqueous solubility, poor tissue absorption, rapid metabolism and short plasma half-life have made curcumin unsuitable for systemic administration for better wound healing. Recently, various topical formulations of curcumin such as films, fibers, emulsion, hydrogels and different nanoformulations have been developed for targeted delivery of curcumin at wounded sites. In this review, we summarize and discuss different topical formulations of curcumin with emphasis on their wound-healing properties in animal models.

Brain Targeting of siRNA via Intranasal Pathway.

Brain diseases are the most serious health problems; represent a significant and worldwide public health problem. Small interfering RNAs (siRNAs) can initiate specific silencing of genes and are potential therapeutic agents for many genetically influenced diseases including brain disease. However, on systemic administration the blood-brain barrier (BBB) poses most significant obstacle for the therapeutic siRNAs delivery to the brain. Therefore, the development of successful approaches to enhance siRNA delivery to the brain is of immense interest in clinical and pharmaceutical research. At present, intranasal delivery approach serves as an effective mode of direct delivery of siRNAs to brain by bypassing BBB. In this review, we describe the principles of RNA interference (RNAi) machinery; challenges associated with siRNAs in therapeutics brain targeting and summarize the recent progress made in the use of vector based siRNA technology. Further, it is anticipated that intranasal delivery approach will have a very important role to play in the future for the translation of siRNAs therapeutics from bench to bedside for different brain diseases.

Antiglioma activity of curcumin-loaded lipid nanoparticles and its enhanced bioavailability in brain tissue for effective glioblastoma therapy.

Glioblastoma, the most aggressive form of brain and central nervous system tumours, is characterized by high rates proliferation, migration and invasion. The major road block in the delivery of drugs to the brain is the blood-brain barrier, along with the expression of various multi-drug resistance (MDR) proteins that cause the efflux of a wide range of chemotherapeutic drugs. Curcumin, a herbal drug, is known to inhibit cellular proliferation, migration and invasion and induce apoptosis of glioma cells. It also has the potential to modulate MDR in glioma cells. However, the greatest challenge in the administration of curcumin stems from its low bioavailability and high rate of metabolism. To circumvent the above pitfalls of curcumin we have developed curcumin-loaded glyceryl monooleate (GMO) nanoparticles (NP) coated with the surfactant Pluronic F-68 and vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for brain delivery. We demonstrated that our curcumin-loaded NPs inhibit cellular proliferation, migration and invasion along with a higher percentage of cell cycle arrest and telomerase inhibition, thus leading to a greater percentage apoptotic cell death in glioma cells compared with native curcumin. An in vivo study demonstrated enhanced bioavailability of curcumin in blood serum and brain tissue when delivered by curcumin-loaded GMO NPs compared with native curcumin in a rat model. Thus, curcumin-loaded GMO NPs can be used as an effective delivery system to overcome the challenges of drug delivery to the brain, providing a new approach to glioblastoma therapy.

Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin.

INTRODUCTION: Curcumin is a safe, affordable and natural bioactive molecule of turmeric (Curcuma longa). It has gained considerable attention in recent years for its multiple pharmacological activities. However, its optimum pharmaceutical potential has been limited by its lack of aqueous solubility and poor bioavailability. To mitigate the above limitations, recently various nanostructured water-soluble delivery systems were developed to increase the solubility and bioavailability of curcumin. AREAS COVERED: Major reasons contributing to the low bioavailability of curcumin appear to be owing to its poor solubility, low absorption, rapid metabolism and rapid systemic elimination. The present review summarizes the strategies using curcumin in various nanocarrier delivery systems to overcome poor solubility and inconsistent bioavailability of curcumin and describes the current status and challenges for the future. EXPERT OPINION: The development of various drug delivery systems to deliver curcumin will certainly provide a step up towards augmenting the therapeutic activity of curcumin thereby increasing the solubility and bioavailability of curcumin. However, the future of such delivery technology will be highly dependent on the development of safe, non-toxic and non-immunogenic nanocarriers.

Nanotechnology-based combinational drug delivery: an emerging approach for cancer therapy.

Combination therapy for the treatment of cancer is becoming more popular because it generates synergistic anticancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. In recent years, nanotechnology-based combination drug delivery to tumor tissues has emerged as an effective strategy by overcoming many biological, biophysical and biomedical barriers that the body stages against successful delivery of anticancer drugs. The sustained, controlled and targeted delivery of chemotherapeutic drugs in a combination approach enhanced therapeutic anticancer effects with reduced drug-associated side effects. In this article, we have reviewed the scope of various nanotechnology-based combination drug delivery approaches and also summarized the current perspective and challenges facing the successful treatment of cancer.

Enhanced cellular uptake and in vivo pharmacokinetics of rapamycin-loaded cubic phase nanoparticles for cancer therapy.

To date cancer is considered as one of the most devastating diseases due to its high rate of mortality. Preclinical studies have demonstrated that the Akt/mTOR (mammalian target of rapamycin) pathway is activated in cancers and inhibition of this pathway has great potential in anti-cancer therapy. Rapamycin, one of the most potent anti-cancer drugs, blocks Akt/mTOR function and has anti-proliferative activity in several cancers. To circumvent problems associated with rapamycin due to its poor water solubility, poor oral bioavailability, low accessibility to cancer tissues and systemic toxicity, rapamycin-loaded cubic nanoparticles (NP) were formulated with vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as an emulsifier for oral delivery. Cubic NP were characterised and these particles demonstrated better cytotoxicity and apoptosis compared with native rapamycin under in vitro conditions due to their enhanced cellular uptake. The molecular impact of particulate systems on the Akt/mTOR pathway were elucidated by immunoblotting. Down-regulation of different anti-apoptotic genes of this pathway indicates activation of apoptotic signals leading to MIA PaCa cell death. An in vivo study demonstrated enhanced bioavailability of rapamycin in cubic NP in comparison with native rapamycin in a mouse model with no toxicity and good biocompatibility of void cubic NP at a higher dose of oral administration. Thus, rapamycin-loaded cubic NP can be used as an effective drug delivery system to produce better rapamycin therapeutics for the treatment of cancers.

Receptor mediated tumor targeting: an emerging approach for cancer therapy.

Receptor-mediated tumor targeting has received major attention in the field of cancer drug delivery in the past few years. Receptors, as molecular target has opened new opportunities for cellular or intracellular targeting of drug loaded delivery systems conjugated with targeting moieties i.e. ligand. This receptor mediated targeting of cancer drug through nano carrier systems to cancerous tissue offer protection and improves the pharmacokinetics of various drugs and help to overcome the systemic toxicity and adverse effects that result from the non-selective nature of most current cancer therapeutic agents. The article reviews the scope of receptor mediated targeting of anticancer drug loaded in various nanocarriers and also summarize recent perspective and challenges in the field of nanocarrier-aided drug delivery and drug targeting for cancer therapy.

The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation.

Curcumin, the natural anticancer drug and its optimum potential is limited due to lack of solubility in aqueous solvent, degradation at alkaline pH and poor tissue absorption. In order to enhance its potency and improve bioavailability, we have synthesized curcumin loaded nanoparticulate delivery system. Unlike free curcumin, it is readily dispersed in aqueous medium, showing narrow size distribution 192 nm ranges (as observed by microscope) with biocompatibility (confocal studies and TNF-alpha assay). Furthermore, it displayed enhanced stability in phosphate buffer saline by protecting encapsulated curcumin against hydrolysis and biotransformation. Most importantly, nanoparticulate curcumin was comparatively more effective than native curcumin against different cancer cell lines under in vitro condition with time due to enhanced cellular uptake resulting in reduction of cell viability by inducing apoptosis. Molecular basis of apoptosis studied by western blotting revealed blockade of nuclear factor kappa B (NFkappaB) and its regulated gene expression through inhibition of IkappaB kinase and Akt activation. In mice, nanoparticulate curcumin was more bioavailable and had a longer half-life than native curcumin as revealed from pharmacokinetics study. Thus, the results demonstrated nanoparticulate curcumin may be useful as a potential anticancer drug for treatment of various malignant tumors.