Browsing by Author "Sajeesh, S."

Now showing 1 - 7 of 7
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    Cyclodextrin complexed insulin encapsulated hydrogel microparticles: An oral delivery system for insulin
    (JOURNAL OF CONTROLLED RELEASE, 2010)
    An oral insulin delivery system based on methyl-beta-cyclodextrin (MCD) complexed insulin encapsulated polymethacrylic acid (PMAA) hydrogel microparticles was evaluated in this investigation. Poly(methacrylic acid)-chitosan-polyethylene glycol (PCP) microparticles were prepared by ionic gelation method. The insulin-MCD (IC) complex prepared was characterized by fluorescence spectroscopic and isothermal titration micro-calorimeteric (ITC) methods. MCD complexed insulin was encapsulated onto PCP microparticles by diffusion filling method. Loading and release properties of the complexed insulin from microparticles were evaluated under in vitro conditions. The effect of MCD complexation on the permeability of insulin was studied using Caco 2 cell monolayers and excised intestinal tissue with an Ussing chamber setup. In vivo experiments were carried on streptozotocin induced diabetic rats to evaluate the efficacy of MCD complexed insulin encapsulated PCP microparticles to deliver insulin by the oral route.IC complex formation was established by fluorescence and ITC investigations. Insulin loading and release properties from the hydrogel matrix was rather unaffected by the MCD complexation. However MCD complexation was effective in enhancing insulin transport across Caco 2 cell monolayers, when applied in combination with the PMAA hydrogel system. Both insulin and MCD complexed insulin encapsulated PCP microparticles were effective in reducing blood glucose level in diabetic animal models. Cyclodextrin complexed insulin encapsulated hydrogel microparticles appear to be an interesting candidate for oral delivery of insulin. (C) 2010 Elsevier B.V. All rights reserved.
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    Cyclodextrin-insulin complex encapsulated polymethacrylic acid based nanoparticles for oral insulin delivery
    (INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2006)
    Present investigation was aimed at developing an oral insulin delivery system based on hydroxypropyl 0 cyclodextrin-insulin (HP beta CD-I) complex encapsulated polymethacrylic acid-chitosan-polyether (polyethylene glycol-polypropylene glycol copolymer) (PMCP) nanoparticles. Nanoparticles were prepared by the free radical polymerization of methacrylic acid in presence of chitosan and polyether in a solvent/surfactant free medium. Dynamic light scattering (DLS) experiment was conducted with particles dispersed in phosphate buffer (pH 7.4) and size distribution curve was observed in the range of 500-800 nm. HP beta CD was used to prepare non-covalent inclusion complex with insulin and complex was analyzed by Fourier transform infrared (FTIR) and fluorescence spectroscopic studies. HP beta CD complexed insulin was encapsulated into PMCP nanoparticles by diffusion filling method and their in vitro release profile was evaluated at acidic/alkaline pH. PMCP nanoparticles displayed good insulin encapsulation efficiency and release profile was largely dependent on the pH of the medium. Enzyme linked immuno sorbent assay (ELISA) study demonstrated that insulin encapsulated inside the particles was biologically active. Trypsin inhibitory effect of PMCP nanoparticles was evaluated using N-alpha-benzoyl-L-arginine ethyl ester (BAEE) and casein as substrates. Mucoadhesive studies of PMCP nanoparticles were conducted using freshly excised rat intestinal mucosa and the particles were found fairly adhesive. From the preliminary studies, cyclodextrin complexed insulin encapsulated mucoadhesive nanoparticles appear to be a good candidate for oral insulin delivery. (c) 2006 Elsevier B.V. All rights reserved.
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    Effect of thiol functionalization on the hemo-compatibility of PLGA nanoparticles
    (JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A, 2011)
    In this study, an attempt was made to reduce the interaction of poly(D, L-lactic acid/glycolic acid) (PLGA) nanoparticles with the opsonins and phagocytic cells upon functionalization with thiol groups. Terminal carboxylic groups in PLGA were conjugated to the amino group of cysteine and nanoparticles were prepared by solvent evaporation technique. Detailed in vitro investigations were performed on PLGA and cysteine modified PLGA (Cys-PLGA) nanoparticles to asses their blood compatibility. The effect of these nanoparticles on the release of proinflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha) from human macrophage cells were evaluated. Thiolation was confirmed by fourier transform infrared spectroscopy and Ellman's assay; both PLGA and modified nanoparticles had average size in the range of 250 nm. Thiolation was an effective strategy in reducing the protein adsorption, complement activation, and platelet activation of PLGA nanoparticles. PLGA and modified PLGA nanoparticles were compatible with the blood cells and no hemolytic effect was detected. Particles were noncytotoxic on L929 cells and release of proinflammatory cytokines from macrophage cells was rather unaffected with the modification strategy. From these studies, it seems that thiolation of particulate delivery system is an interesting approach in manipulating the blood-particle interactions and appears to be an effective candidate for injectable drug delivery applications. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 607-617, 2011.
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    Mucoadhesive hydrogel microparticles based on poly (methacrylic acid-vinyl pyrrolidone)-chitosan for oral drug delivery
    (DRUG DELIVERY, 2011)
    The study was aimed at the evaluation of N-vinyl pyrrolidone (NVP) incorporated polymethacrylic acid-chitosan microparticles for oral drug delivery applications. Poly (methacrylic acid)-chitosan (PMC) and poly(methacrylic acid-vinyl pyrrolidone)-chitosan (PMVC) microparticles were prepared by an ionic-gelation method. Mucoadhesion behaviour of these particles was evaluated by ex-vivo adhesion method using freshly excised rat intestinal tissue. Cytotoxicity and absorption enhancing property of PMC and PMVC particles were evaluated on Caco 2 cell monolayers. Protease enzyme inhibition capability and insulin loading/release properties of these hydrogel particles was evaluated under in vitro experimental conditions. Addition of NVP units enhanced the mucoadhesion behavior of PMC particles on isolated rat intestinal tissue. Both PMC and PMVC particles were found non-toxic on Caco 2 cell monolayers and PMC particles was more effective in improving paracellular transport of fluorescent dextran across Caco 2 cell monolayers as compared to PMVC particles. However, protease inhibition efficacy of PMC particles was not significantly affected with NVP addition. NVP incorporation improved the insulin release properties of PMC microparticles at acidic pH. Hydrophilic modification seems to be an interesting approach in improving mucoadhesion capability of PMC microparticles.
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    Novel polyelectrolyte complexes based on poly(methacrylic acid)-bis(2-aminopropyl)poly(ethylene glycol) for oral protein delivery
    (JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, 2007)
    In the present investigation a simple and effective strategy was employed for the development of pH-sensitive self-assembling microparticles based on poly(methacrylic acid) (PMAA)-bis(2-aminopropyl)poly(ethylene glycol) (APEG), and their efficiency in oral protein delivery was evaluated. An inter-ionic gelation process was employed for the preparation of microparticles and particles were obtained spontaneously during the process without using any surfactants or stabilizers. Particle size analysis was carried out to measure average particle size and surface morphology was evaluated using scanning electron microscopy (SEM). Bovine serum albumin (BSA) was incorporated onto these microparticles to evaluate the loading and release properties of the matrix. PMAA-APEG microparticles displayed pH responsive release profile, as less than 10% of encapsulated BSA was released at pH 1.2 in 2 h and more than 80% of loaded protein was released within 3 h at pH 7.4. Carboxymethyl beta-cyclodextrin (CM beta CD)-insulin non-covalent inclusion complex was prepared to enhance the stability of insulin formulations and complex formation was analyzed by fluorescence spectroscopic studies. CM beta CD-complexed insulin was encapsulated into PMAA-APEG microparticles by a diffusion filling method and biological activity of entrapped insulin was evaluated using an ELISA. Finally mucoadhesive studies of PMAA-APEG microparticles were carried out on freshly excised rat intestinal mucosa at neutral pH to establish the adhesive nature of the material.
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    Surface-functionalized polymethacrylic acid based hydrogel microparticles for oral drug delivery
    (EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2010)
    Aim of the present work was to develop novel thiol-functionalized hydrogel microparticles based on poly(methacrylic acid)-chitosan-poly(ethylene glycol) (PCP) for oral drug delivery applications.PCP microparticles were prepared by a modified ionic gelation process in aqueous medium. Thiol modification of surface carboxylic acid groups of PCP micro particles was carried out by Coupling L-Cysteine with a water-soluble carbodiimide. Ellman's method was adopted to quantify the sulfhydryl groups. and dynamic light-scattering technique was used to measure the average particle size. Cytotoxicity of the modified particles was evaluated on Caco 2 cells by MTT assay. Effect of thiol modification on permeability of paracellular marker fluorescence dextran (FD4) was evaluated on Caco 2 cell monolayers and freshly excised rat intestinal tissue with an Ussing chamber set-up. Mucoadhesion experiments were carried out by an ex vivo bioadhesion method with excised rat intestinal tissue.The average size of the PCP microparticles was increased after thiol modification. Thiolated microparticles significantly improved the paracellular permeability of FD4 across Caco 2 cell monolayers, with no sign of toxicity. However, the efficacy of thiolated system remained low when permeation experiments were carried out across excised intestinal membrane. This was attributed to the high adhesion of the thiolated particles on the gut mucosa. Nevertheless, it can be concluded that surface thiolation is an interesting strategy to improve paracellular permeability of hydrophilic macromolecules. (C) 2009 Elsevier B.V. All rights reserved.
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    Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery
    (ACTA BIOMATERIALIA, 2010)
    In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles From these studies thiolation of hydrogel microparticles seems to be a promising approach to Improve oral delivery of proteins/peptides (C) 2010 Acta Materialia Inc Published by Elsevier Ltd All rights reserved