Institute of Life science

Bhubaneshwar, India

Institute of Life science

Bhubaneshwar, India
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Parhi P.,Institute of Life science | Mohanty C.,Institute of Life science | Sahoo S.K.,Institute of Life science
Drug Discovery Today | Year: 2012

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. © 2012 Elsevier Ltd. All rights reserved.


Misra R.,Institute of Life science | Sahoo S.K.,Institute of Life science
European Journal of Pharmaceutical Sciences | Year: 2010

Doxorubicin (DOX) is an anticancer drug with an intracellular site of action in the nucleus. For high antitumour activity, it should be effectively internalized into the cancer cells and accumulate in the nucleus. In this study, we have prepared a nuclear localization signal conjugated doxorubicin loaded Poly (d,l-lactide-co-glycolide) nanoparticles (NPs), to deliver doxorubicin to the nucleus efficiently. Physico-chemical characterization of these NPs showed that the drug is molecularly dispersed in spherical and smooth surfaced nanoparticles. NPs (∼226 nm in diameter, 46% encapsulation efficiency) under in vitro conditions exhibited sustained release of the encapsulated drug (63% release in 60 days). Cell cytotoxicity results showed that NLS conjugated NPs exhibited comparatively lower IC50 value (2.3 μM/ml) than drug in solution (17.6 μM/ml) and unconjugated NPs (7.9 μM/ml) in breast cancer cell line MCF-7 as studied by MTT assay. Cellular uptake studies by confocal laser scanning microscopy (CLSM) and fluorescence spectrophotometer showed that greater amount of drug is targeted to the nucleus with NLS conjugated NPs as compared to drug in solution or unconjugated NPs. Flow cytometry experiments results showed that NLS conjugated NPs are showing greater cell cycle (G2/M phase) blocking and apoptosis than native DOX and unconjugated NPs. In conclusion, these results suggested that NLS conjugated doxorubicin loaded NPs could be potentially useful as novel drug delivery system for breast cancer therapy. © 2009 Elsevier B.V. All rights reserved.


Acharya S.,Institute of Life science | Sahoo S.K.,Institute of Life science
Advanced Drug Delivery Reviews | Year: 2011

As mortality due to cancer continues to rise, advances in nanotechnology have significantly become an effective approach for achieving efficient drug targeting to tumour tissues by circumventing all the shortcomings of conventional chemotherapy. During the past decade, the importance of polymeric drug-delivery systems in oncology has grown exponentially. In this context, poly(lactic- co-glycolic acid) (PLGA) is a widely used polymer for fabricating 'nanoparticles' because of biocompatibility, long-standing track record in biomedical applications and well-documented utility for sustained drug release, and hence has been the centre of focus for developing drug-loaded nanoparticles for cancer therapy. Such PLGA nanoparticles have also been used to develop proteins and peptides for nanomedicine, and nanovaccines, as well as a nanoparticle-based drug- and gene-delivery system for cancer therapy, and nanoantigens and growth factors. These drug-loaded nanoparticles extravasate through the tumour vasculature, delivering their payload into the cells by the enhanced permeability and retention (EPR) effect, thereby increasing their therapeutic effect. Ongoing research about drug-loaded nanoparticles and their delivery by the EPR effect to the tumour tissues has been elucidated in this review with clarity. © 2010 Elsevier B.V.


Parveen S.,Institute of Life science | Sahoo S.K.,Institute of Life science
European Journal of Pharmacology | Year: 2011

Polymeric nanoparticles have long been sought after as carriers for systemic and targeted drug delivery. The ability of these particles to circulate in the bloodstream for a prolonged period of time is often a prerequisite for successful targeted delivery. To achieve this, paclitaxel loaded chitosan and polyethylene glycol coated PLGA (PLGA-CS-PEG) nanoparticles were formulated and characterized that could efficiently encapsulate hydrophobic drugs, and also evade the phagocytic uptake by reducing opsonization by blood proteins, hence increasing the bioavailability of the drug. In our study, we primarily assessed a rational approach for designing and formulating ideal long-circulating nanoparticles by optimizing the concentration of chitosan (CS) and polyethylene glycol (PEG). Uptake efficiency and in vitro cytotoxicity of the formulated nanoparticles was also evaluated in different cancer cell lines (retinoblastoma, breast cancer and pancreatic cancer). PLGA-CS-PEG nanoparticles showed dramatic prolongation in blood circulation, as well as reduced macrophage uptake, with only a small amount of the nanoparticles sequestered in the liver, when compared to PLGA-CS and PLGA nanoparticles. Superior anti-proliferative effect and cell cycle inhibition was observed in case of PLGA-CS nanoparticles and PLGA-CS-PEG nanoparticles over PLGA nanoparticles and native paclitaxel, which may be due to higher cellular uptake resulting in greater antiproliferative activity of nanoparticles. The present results thus suggest that, a combinational coating of PEG and chitosan may represent a significant step in the development of long-circulating drug delivery carriers for tumor drug delivery. © 2011 Elsevier B.V. All rights reserved.


Veiga-Parga T.,University of Tennessee at Knoxville | Sehrawat S.,Institute of Life science | Rouse B.T.,University of Tennessee at Knoxville
Immunological Reviews | Year: 2013

The host response to viruses includes multiple cell types that have regulatory function. Most information focuses on CD4+ regulatory T cells that express the transcription factor Foxp3+ (Tregs), which are the topic of this review. We explain how viruses through specific and non-specific means can trigger the response of thymus-derived natural Tregs as well as induce Tregs. The latter derive under appropriate stimulation conditions either from uncommitted precursors or from differentiated cells that convert to become Tregs. We describe instances where Tregs appear to limit the efficacy of antiviral protective immunity and other, perhaps more common, immune-mediated inflammatory conditions, where the Tregs function to limit the extent of tissue damage that occurs during a virus infection. We discuss the controversial roles that Tregs may play in the pathogenesis of human immunodeficiency and hepatitis C virus infections. The issue of plasticity is discussed, as this may result in Tregs losing their protective function when present in inflammatory environments. Finally, we mention approaches used to manipulate Treg numbers and function and assess their current value and likely future success to manage the outcome of virus infection, especially those that are responsible for chronic tissue damage. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Mohanty C.,Institute of Life science | Sahoo S.K.,Institute of Life science
Biomaterials | Year: 2010

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-α 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 (NFκB) and its regulated gene expression through inhibition of IκB 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. © 2010 Elsevier Ltd.


Bharati A.,Institute of Life science
PloS one | Year: 2012

Artemisinin, a secondary metabolite produced in Artemisia plant species, besides having antimalarial properties is also phytotoxic. Although, the phytotoxic activity of the compound has been long recognized, no information is available on the mechanism of action of the compound on photosynthetic activity of the plant. In this report, we have evaluated the effect of artemisinin on photoelectron transport activity of chloroplast thylakoid membrane. The inhibitory effect of the compound, under in vitro condition, was pronounced in loosely and fully coupled thylakoids; being strong in the former. The extent of inhibition was drastically reduced in the presence of uncouplers like ammonium chloride or gramicidin; a characteristic feature described for energy transfer inhibitors. The compound, on the other hand, when applied to plants (in vivo), behaved as a potent inhibitor of photosynthetic electron transport. The major site of its action was identified to be the Q(B); the secondary quinone moiety of photosystemII complex. Analysis of photoreduction kinetics of para-benzoquinone and duroquinone suggest that the inhibition leads to formation of low pool of plastoquinol, which becomes limiting for electron flow through photosystemI. Further it was ascertained that the in vivo inhibitory effect appeared as a consequence of the formation of an unidentified artemisinin-metabolite rather than by the interaction of the compound per se. The putative metabolite of artemisinin is highly reactive in instituting the inhibition of photosynthetic electron flow eventually reducing the plant growth.


Singh A.,Institute of Life science | Sahoo S.K.,Institute of Life science
Drug Discovery Today | Year: 2014

Multifunctional nanoplatforms represent a cutting edge tool in biomedical applications as a result of their applicability in the concurrent monitoring of medical treatment. Magnetic nanoparticles (MNPs) have generated great interest in the field of cancer nanotheranostics owing to their intrinsic magnetic property that enables them to be used as contrast agents in magnetic resonance imaging and as a therapeutic system in conjunction with hyperthermia. In addition, the physical properties and biocompatibility of MNPs help them to act as efficient drug carriers for targeted therapeutic regimes. In this review, we have discussed the different theranostic applications of MNPs. Further, we have raised the current challenges associated with the clinical translation of MNPs along with future opportunities in this field. © 2013 Elsevier Ltd.


Misra R.,Institute of Life science | Sahoo S.K.,Institute of Life science
Molecular Pharmaceutics | Year: 2011

Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic used to treat a variety of cancers including leukemia. Chronic myeloid leukemia (CML) blasts like K562 cells are resistant to apoptosis induced by DOX due to several reasons, the primary being the sequestration of drug into cytoplasmic vesicles and induction of multidrug resistance (MDR) gene expression with DOX treatment resulting in intracellular resistance to this drug. Moreover, expression of antiapoptotic protein BCL-2 and the hybrid gene bcr/abl in K562 cells contributes resistance to DOX. Studies have shown that curcumin (CUR) has a pleiotropic therapeutic effect in cancer treatment, as it is an inhibitor of nuclear factor kappa B (NFκB) as well as a potent downregulator of MDR transporters. In this study, we investigated the potential benefit of using DOX and CUR in a single nanoparticle (NP) formulation to inhibit the development of drug resistance for the enhancement of antiproliferative activity of DOX in K562 cells. Results illustrate that the dual (DOX+CUR) drug loaded NPs were effectively delivered into K562 cells. CUR not only facilitates the retention of DOX in nucleus for a longer period of time but also inhibits the gradual expression of MDR1 and BCL-2 at the mRNA level in K562 cells. Moreover, Western blot results confirm that in combination both of the drugs were capable of inducing apoptosis even if in a lower concentration compared to either single drug in both solution or in formulation. Combinational therapy by using DOX and CUR, especially when administered in the NP formulation, has enhanced the cytotoxicity in K562 cells by promoting the apoptotic response. Overall, this combinational strategy has significant promise in the clinical management of intractable diseases, especially leukemia. © 2011 American Chemical Society.


Patent
Institute Of Life Science | Date: 2013-03-15

The present invention is an aqueous dispersible magnetic nanoparticle formulation with a high drug loading capacity used for sustained drug delivery. The formulated magnetic nanoparticles are composed of an iron oxide core coated with a long chain polymer, which provides aqueous dispersibility without the use of surfactant. A method is developed for the functionalization of magnetic nanoparticles for use in biomedical field.

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