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ABSTRACT: Highly sensitive, selective and mediator-free electrochemical biosensor with nano-interface for sensing xanthine using xanthine oxidase (XOx) has been developed. Towards the preparation of nano-interface, Fe3O4 nanoparticles were synthesized by thermal co-precipitation method and structural, morphological characterizations were carried out using X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM) and field emission transmission electron microscope (FE-TEM) respectively. The modified electrode with the covalently linked XOx was confirmed by FT-IR. With the modified electrode as working electrode, electrochemical studies were carried out. The linear range was found to be from 0.4 to 2.4nM. The biosensor exhibited an optimum response in less than 2s and was not prone to interferences from ascorbic acid, urea and sucrose. The Michaelis-Menten constant (Km) was found to be 1.3nM. The limit of detection is found to be 2.5pM and limit of quantification as 8.3pM. The developed biosensor was used for the real time measurement of fish freshness.
Food Chemistry 08/2013; 139(1-4):963-9. · 3.65 Impact Factor
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ABSTRACT: Alzheimer's disease, is a neuro-degenerative disease affecting millions of people worldwide. The proteolytic cleavage of amyloid precursor protein forms amyloid beta peptide (Aβ1-42), which aggregates to form senile plaques. The KLVFF motif present in the Aβ1-42 is essential for aggregation. Curcumin, a prinicipal curcuminoid present in turmeric, shows therapeutic activity against Alzheimer's disease. However, the nature of interaction between the Aβ1-42 peptide and curcumin remains unexplored. Studies on the interaction of the core-recognition motif KLVFF with curcumin can be extrapolated to decipher the interactions between Aβ1-42 and curcumin. Our data shows curcumin and KLVFF interact strongly through hydrophobic forces and stabilized by hydrogen bonding. The hydrophobic interactions were confirmed from the positive shift in the phase transition temperature. Fluorescence quenching studies demonstrate a static quenching mechanism. FTIR data confirms the beta sheet breaking ability of curcumin, which is also substantiated by cell culture studies.
Journal of Agricultural and Food Chemistry 03/2013; · 2.82 Impact Factor
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Macromolecular Research 02/2013; · 1.15 Impact Factor
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Sensors and Actuators B Chemical 02/2013; 176:884-892. · 3.90 Impact Factor
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ABSTRACT: Parkinson's is a major neurodegenerative disorder that occurs due to loss of dopaminergic neurons in basal ganglia. Conventional therapy includes surgery that involves lot of risk and administration of levodopa which is accompanied by poor bioavailability, short half-life, and side effects. In the present study, poly(butylene succinate) (PBSu) microspheres-based drug delivery system to improve the bioavailability of the drug levodopa was evaluated for the first time. Biodegradable porous and smooth PBSu microspheres were prepared by double emulsion solvent evaporation technique (W/O/W) and the effect of solvent and surfactant was studied. The maximum encapsulation efficiency achieved was 53.93% and 62.28% for porous and smooth microspheres, respectively. In vitro drug release was studied in phosphate buffered saline and simulated CSF buffer of pH 7.4. Initially a burst effect followed by sustained release of drug was obtained for about 32 h and 159 h for porous and smooth microspheres, respectively. The release rate was higher in simulated CSF when compared with PBS, due to higher concentration of sodium ions and cations in simulated CSF. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.
Journal of Biomedical Materials Research Part B Applied Biomaterials 02/2013; · 2.15 Impact Factor
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ABSTRACT: Tissue engineering requires an ideal scaffold that will aid in the regeneration of the damaged tissues both structurallyand functionally. Conventionally, polymeric nanofibrous scaffolds have been extensively used due to their structuralsimilarity to the native extracellular matrix. Thus far, top-down approaches like electrospinning and phase separationhave been predominantly used for the nanofiber fabrication. Recently, self-assembling peptide nanofibers (SAPNF) havebeen identified as promising scaffolds for tissue engineering applications. Molecular self-assembly of peptides, which is abottom-up approach has laid foundations for the development of such novel scaffolds. Designer self-assembling peptidesprovide functional support as well as bio-recognition due to the presence of bioactive motifs embedded in them. However,there are certain limitations to both electrospun and SAPNF scaffolds in terms of synthesis, cues presented to the biologicalsystem and applications. Design of composite, hybrid scaffolds by super-positioning possible cues may result in effectivefunctional tissue regeneration at multiple levels.
Current Protein and Peptide Science 02/2013; 14(1):70-84. · 2.89 Impact Factor
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ABSTRACT: Molecular self-assembly of biomolecules, especially proteins and peptides has elucidated much interest in recent years due to the reproducibility of structures and the high degree of control on the formation kinetics and morphology by varying the self-assembling conditions. These self-assembled structures have found widespread applications in tissue engineering, drug delivery and electronics. Two pentapeptides, namely Soto peptide (LPFFD) and the Tjernberg peptide (KLVFF), have been proposed to effectively curtail amyloid plaque deposits. Being amphipathic, these molecules can undergo self-assembly that can be influenced by a host of factors including concentration, pH, proteins, salt content, etc. However, this facet is scarcely explored till date, which might pave way for the novel treatment strategy for Alzheimer's disease. Our data show that the peptide spontaneously forms micelles and they are rich in beta sheet structures, which is confirmed using FT-IR, SAED and thioflavin binding studies. While, acidic pH seems to have no role in the formation of higher order structures, alkaline pH promotes longitudinal and lateral stacking interactions resulting in formation of higher order structures. We also found that the hydrophobicity and hydrophilicity of the substrate also play a major role in the formation of higher order structures. Moreover, the micelles formed by the KLVFF peptide under various environmental conditions exhibits excellent surface tension lowering effects which is in good agreement with the cell proliferation data that showed the protective ability of KLVFF peptide against Aβ1–42 cytotoxicity indicating its potential in Alzheimer's disease therapy as an aggregation blocking agent.
Soft Matter 01/2013; 9(9):2684-2694. · 4.39 Impact Factor
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ABSTRACT: The present study investigates dose-dependent effects of trans-resveratrol on the membrane fluidity using planar lipid bilayer and liposome models. The complex admittance plots obtained for the lipid bilayer show that resveratrol, below 60 M preferentially interacts with the polar head groups at the membrane-electrolyte interface leading to enhanced membrane admittance and vice versa at higher concentrations (> 60 µM). This was confirmed using solid-state 13C and 31P NMR studies and membrane fluidization studies. The localization of resveratrol in the membrane bilayer was found to alter the membrane rigidity, which resulted in a dose-dependent blebbing and lysis of erythrocytes. The protective effect of trans-resveratrol against DPPH also confirms that its localization in the hydrophobic region prevents lipid peroxidation. The cytotoxic effect of resveratrol on a breast cancer cell line also displays a progressive pattern, indicating possible correlation with its membrane rigidifying properties and localization in the lipid bilayer.
Journal of Medicinal Chemistry 01/2013; · 4.80 Impact Factor
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Materials Chemistry and Physics 01/2013; 137:892-897. · 2.23 Impact Factor
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Journal of Porous Materials 01/2013; · 1.24 Impact Factor
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ABSTRACT: On the basis of a thermal process, a facile, low cost, one-step approach for preparing iron oxide (Fe(2)O(3)) incorporated ordered magnetic mesoporous silica nanocomposites by a co-operative self-assembly approach is presented. Various mesostructured silica materials incorporated with different amounts of iron oxide (nSi/nFe = 1/1, 1/0.5, 1/0.25 and 1/0.123) at various pH (<1, 3, 5 and 7) were synthesized and characterized by electron microscopy and X-ray diffractometry. Further, the surface area and magnetic properties were evaluated using N(2)-sorption analyses, and a superconducting quantum interference device interfaced with a vibrating sample magnetometer (SQUID-VSM) respectively. The transmission electron micrographs and nitrogen sorption analysis indicated that most of the Fe(2)O(3) domains of several nanometers were embedded in the silica walls, rather than dispersed in the mesopores. The incorporation of iron oxide into the mesopores without compromising the structural and textural properties was achieved at pH < 1. These structures have great potential in diagnostics and therapeutics. However, the acceptance of this material by the biological host is a critical issue for such biomedical applications. In this study, we have also evaluated the in vivo biocompatibility of these magnetic mesoporous materials in a rat model. The histopathological results show that this magnetic material can be classified as a level 2 biomaterial that can be safely used for short term applications such as MRI imaging, hyperthermia, targeted drug delivery, etc.
Dalton Transactions 09/2012; 41(40):12530-7. · 3.84 Impact Factor
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ABSTRACT: Introduction: A thorough understanding of the cellular and muscle fiber orientation in left ventricular cardiac tissue is of paramount importance for the generation of artificial cardiac patches to treat the ischemic myocardium. The major challenge faced during cardiac patch engineering is to choose a perfect combination of three entities; cells, scaffolds and signaling molecules comprising the tissue engineering triad for repair and regeneration. Areas covered: This review provides an overview of various scaffold materials, their mechanical properties and fabrication methods utilized in cardiac patch engineering. Stem cell therapies in clinical trials and the commercially available cardiac patch materials were summarized in an attempt to provide a recent perspective in the treatment of heart failure. Various tissue engineering strategies employed thus far to construct viable thick cardiac patches is schematically illustrated. Expert opinion: Though many strategies have been proposed for fabrication of various cardiac scaffold materials, the stage and severity of the disease condition demands the incorporation of additional cues in a suitable scaffold material. The scaffold may be nanofibrous patch, hydrogel or custom designed films. Integration of stem cells and biomolecular cues along with the scaffold may provide the right microenvironment for the repair of unhealthy left ventricular tissue as well as promote its regeneration.
Expert opinion on biological therapy 09/2012; · 3.22 Impact Factor
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ABSTRACT: Gene silencing has emerged as a promising strategy for molecular therapy of various malignant, viral, hereditary and inflammatory disorders. However, its translation from lab to clinic is yet to gain momentum due to the numerous problems that plague its development. A multi-functional siRNA delivery system with desired properties such as enhanced immune compatibility, target specificity, high cell uptake and excellent silencing efficiency is required to understand the challenges involved in the selection and modification of small interfering RNA (siRNA), factors influencing the complexation process and the response of the biological system to the formulation. Liposomes have been used as delivery systems due to its versatility in handling different types of drugs, tunable size, charge and surface functionalities that improve its effectiveness in vivo. This review highlights the challenges involved in gene silencing and describes the progression of liposomal systems used in gene silencing. The rationale in introducing chemical modifications in siRNA, synthesizing designer cationic lipids and evolution of hybrid liposomal systems has been elaborated, emphasizing their merits and short-comings. Finally, a description of the current state of clinical trials involving liposomal formulations has been included to provide an unbiased perspective of the future of liposomal systems and gene silencing tools as therapeutic tools.
Current Gene Therapy 08/2012; 12(4):315-32. · 3.39 Impact Factor
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Alzheimer's & dementia: the journal of the Alzheimer's Association 07/2012; 8(4):P705. · 5.90 Impact Factor
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ABSTRACT: Biodegradable polymers have been extensively used as scaffolds to regenerate lost tissues. The geometry of the three-dimensional (3D) scaffolds has an influence on the cellular behaviour. In this study, we have developed 3D-scaffolds of axially aligned nanofibres of poly(lactic acid) (PLA), poly(caprolactone) (PCL) and PLA:CL (50:50) with diameters in the range 100-400 nm, internal diameter 4 mm, length 4 cm and wall thickness 0.2 mm, by using a dynamic collector. PCL and PLA:CL nanofibres were significantly less hydrophobic than PLA nanofibres. The porosity of PCL (16.23 ± 9.88%) and PLA:CL nanofibres (14.77 ± 3.41%) were comparable, while PLA (6.57 ± 1.54%) nanofibres had lower porosity. The tensile strength and Young's modulus of PLA was significantly lower than PCL and PLA:CL nanofibres and the suture retention strengths of all three scaffolds were comparable. After 4 weeks, the molecular weight of PLA nanofibres was reduced by 53% compared to 44% and 41% for PCL and the PLA:CL nanofibres, respectively. However, the PLA:CL nanofibres maintained their structural integrity even after 28 days. Platelet adhesion studies showed that PCL nanofibres had least tendency to be thrombogenic, while PLA:CL blend nanofibres were highly thrombogenic. Further, in vitro responses such as cell adhesion, proliferation and gene expression of human umbilical vascular endothelial cells (HUVECs) were evaluated. After 6 days of culture, the surfaces of all the three scaffolds were completely covered with cells. Our results demonstrate that expression levels of elastin, angiopoietin, laminin-4α and -5α were upregulated in PCL and PLA:CL nanofibres without the addition of any exogenous factors. Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Tissue Engineering and Regenerative Medicine 07/2012; · 3.28 Impact Factor
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ABSTRACT: The investigation of chemotherapeutic agents for the treatment of cancer since the early 1940s has resulted in the discovery of over 50 drugs till date. However, most of these drugs result in severe side effects causing physical and mental trauma to patients. In order to eliminate the side effects, search for better and safer drugs has been ongoing for several decades, which has resulted in the discovery of anti�cancer properties of many phytochemicals. Polyphenols represent a unique class of phytochemicals that possess excellent anti�oxidant, anti�inflammatory properties and also modulate cell signalling pathways leading to anti�cancer effects. However, the use of these compounds as anti�cancer agents is not as effective and hence combinations of chemotherapeutic drugs with these molecules have been attempted. Promising results in in vitro and in vivo experiments while using combinations of polyphenols and chemotherapeutic agents open up new avenues for the discovery of the ideal drug combinations for cancer therapy. This review highlights the efficacy of the combination of phytochemicals with synthetic anti�neoplastic drugs over the conventional combinations of anti�neoplastic drugs and the possible interventions in the clinical settings. The review also discusses the inclusion of polyphenols in emerging therapeutic modalities like nanotechnology and photodynamic therapy.
Anti-cancer agents in medicinal chemistry 06/2012;
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ABSTRACT: Electrospun nanofibrous scaffolds have received a great deal of attention in tissue engineering in recent years. Bridging larger nerve gaps between proximal and distal ends requires exogenous tubular constructs with uniaxially aligned topographical cues to promote the axonal re-growth due to the lack of fibrin cable formation. In this study, we have designed and developed a collector to obtain aligned nanofibers of PLGA-PCL. The average diameter of the fibers obtained is 230 ± 63 nm and the alignment of fibers is quantified by calculating relative angle of each fiber. The tensile strength, porosity, contact angle, and biodegradation of the uniaxial PLGA-PCL nanofibers are measured and compared with the corresponding random fibers. Pore size, Young's modulus, and degradation of the aligned scaffold are significantly lesser than random fibers (p < 0.05). The in vitro cell adhesion and proliferation of Schwann cells on the aligned nanofibers are evaluated and compared with random nanofibers. Our results demonstrate that the alignment of nanofibers has a significant influence on the adhesion and proliferation of Schwann cells. Thus, the axially aligned nanofibers may mimic the fibrin cable architecture; thereby it may represent an ideal scaffold for extending the growth of axonal processes.
Annals of biomedical engineering 05/2012; 40(10):2098-110. · 2.41 Impact Factor
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ABSTRACT: Electrospinning is a versatile technique to make biomimetic and nanostructured scaffolds for skin tissue engineering. In this study we have electrospun and characterized chitosan (C)-poly(vinyl alcohol) (PVA) blend nanofibers as dermal substitutes and compared with 2D C-PVA films. The in vitro characterization of the C-PVA nanofibers and 2D films were evaluated using mouse 3T3 fibroblast cells and our results demonstrated that the cells adhered and proliferated on the surface of C-PVA nanofibers. In our animal studies, the implantation of C-PVA nanofibers along with topical administration of growth factor R-Spondin 1 on full thickness wounds created on rats showed 98.6% wound closure after two weeks post-surgery. The catalase and superoxide dismutase activity of the healing tissue was significantly higher in the groups treated with topical administration of growth factor and C-PVA nanofibers (p < 0.05). Thus these C-PVA nanofibers along with novel growth factor are promising new biomaterials that could be used as dermal substitutes for accelerated wound healing.
Biomedical Materials 05/2012; 7(4):045005. · 2.16 Impact Factor
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ABSTRACT: Current liver transplantation strategies face severe shortcomings owing to scarcity of donors, immunogenicity, prohibitive costs and poor survival rates. Due to the lengthy list of patients requiring transplant, high mortality rates are observed during the endless waiting period. Tissue engineering could be an alternative strategy to regenerate the damaged liver and improve the survival and quality of life of the patient. The development of an ideal scaffold for liver tissue engineering depends on the nature of the scaffold, its architecture and the presence of growth factors and recognition motifs. Biomimetic scaffolds can simulate the native extracellular matrix for the culture of hepatocytes to enable them to exhibit their functionality both in vitro and in vivo. This review highlights the physiology and pathophysiology of liver, the current treatment strategies, use of various scaffolds, incorporation of adhesion motifs, growth factors and stem cells that can stabilize and maintain hepatocyte cultures for a long period.
Biotechnology advances 05/2012; 30(3):742-52. · 8.25 Impact Factor
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ABSTRACT: Although anti-retroviral therapy is the most efficient disease management strategy for HIV-AIDS, its applications are limited by several factors including the low bioavailability and first pass metabolism of the drugs. Nanocarriers such as liposomes have been developed to circumvent some of these problems. We report here preparation of novel liposome formulations for efficient delivery of anti-retroviral drugs to mammalian cells in culture. The liposomes were prepared and surface was modified using poly (ethylene glycol). Encapsulation efficiency of the anti-retroviral drug saquinavir was found to be approximately 33% and also exhibited sustained release of the drug. Although PEGylated liposomes were more stable in protein-supplemented media, had better colloidal stability and exhibited lesser sonochemical stability due to lower cavitation threshold. The cell viability studies using Jurkat T-cells revealed that the PEGylated liposomes loaded with saquinavir were less cytotoxic as compared to the non-PEGylated liposomes or free drug confirming the potential of the liposomes as a sustained drug-release system. The drug delivery potential of the liposomes loaded with Alexa flour 647 was evaluated using Jurkat T-cells and flow cytometry showing uptake upto 74%. Collectively, our data demonstrate efficient targeting of mammalian cells using novel liposome formulations with insignificant levels of cytotoxicity.
International journal of pharmaceutics 04/2012; 431(1-2):120-9. · 2.96 Impact Factor
