Browsing by Author "Sajeesh, S"
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Item Biomimetic mucin modified PLGA nanoparticles for enhanced blood compatibility(JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2013) Thasneem, YM; Rekha, MR; Sajeesh, S; Sharma, CPEfforts to develop long circulating polymeric nanoparticles have propelled many strategies in nanoparticle surface modification to bypass immune surveillance and systemic clearance. In this context, our present study reports on the preparation and evaluation of mucin functionalized poly lactic-co-glycolic acid (PLGA) nanoparticles as hemocompatible, cell penetrating nanoparticulate drug delivery system. Amino groups of mucin were conjugated to the terminal carboxylic acid groups on PLGA to be followed by nanoparticle synthesis via standard solvent evaporation technique. Detailed in vitro experiments were performed to illustrate the significance of alternating copolymer structured mucin modified PLGA nanoparticles in terms of enhanced hemocompatibility and cellular uptake. Mucylation proved promising in controlling PLGA nanoparticle- interaction with plasma proteins (opsonins) and blood components via hemolysis, thrombogenecity and complement activation. Besides hemocompatibility, the modified and unmodified nanoparticles were also found to be cytocompatible with L929 and C6 cell lines. The fluorescent and confocal image analysis evaluated the extent of cellular uptake of nanoparticles into C6 cells. Specifically the combination of stealth properties and cellular internalization capacity of mucin modified PLGA nanoparticle (PLGA Mucin) lead us to propose it as a safe, efficient and multifunctional nanoplatform for disease specific intravenous drug delivery applications as far as in vitro experiments are concerned. (C) 2013 Elsevier Inc. All rights reserved.Item Glucosylated polymeric nanoparticles: A sweetened approach against blood compatibility paradox(COLLOIDS AND SURFACES B-BIOINTERFACES, 2013) Thasneem, YM; Sajeesh, S; Sharma, CPSurface functionalization strategies in generating stealth nano-carriers have garnered considerable attention in pharmaceutical research. In this regard, our investigation reports on the preparation and evaluation of glucose decorated poly lactic-co-glycolic acid (PLGA) nanoparticles as blood compatible nanoparticulate drug delivery system, with enhanced cellular uptake. Terminal carboxylic acid groups on PLGA were modified with the amino group of glucosamine and nanoparticles were generated by modified solvent diffusion (nano-precipitation) technique. Detailed in vitro experiments were performed to evaluate the eminence of glucose functionalization over unmodified nanoparticles, in terms of their hemocompatibility and cellular uptake. Glucosylation was confirmed by NMR and FTIR spectroscopy; PLGA and modified particles had average size in the range of 125 nm. Glucosylation was an effective strategy in reducing plasma protein adsorption, complement activation and platelet plugging of PLGA nanoparticles. PLGA and their glucose modified versions were quite compatible with the blood cells and were non-cytotoxic. Moreover the uptake behaviour of glucose modified PLGA nanoparticles were enhanced in comparison to standard PLGA nanoparticles as emphasized by the z stacking analysis following confocal imaging. Precisely the stealth properties of glucose modified PLGA nanoparticles (PLGA-Glu), with enhanced cellular internalization, seems to be a safe and efficient system for intravenous drug delivery applications. (c) 2013 Elsevier B.V. All rights reserved.Item Interpolymer complex microparticles based on polymethacrylic acid-chitosan for oral insulin delivery(JOURNAL OF APPLIED POLYMER SCIENCE, 2006) Sajeesh, S; Sharma, CPIn the present Study, microparticles composed of polymethacrylic acid-chitosan (PMAA-CS) were prepared by a novel interionic gelation method. Free-radical polymerization of rnethacrylic acid was carried out in the presence of CS, using a water-soluable initiator, and application of these microparticles toward oral insulin delivery was evaluated. Microparticles obtained were characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) Studies. From SEM studies, it was observed that microparticles had an aggregated morphology with size similar to 20 mu m, while FTIR confirmed the presence of ionic interaction between PMAA and CS chains. Protein loading was done by diffusion filling method, and from in vitro release study, it was observed that insulin-loaded microparticles displayed a pH depended release profile at alkaline/acidic pH. Microparticles exhibited Sustained release Of insulin for 3-4 h at neutral pH, and enzyme linked immunosorbent assay (ELISA) proved that encapsulated protein maintained 100% biological activity at neutral pH. Preliminary study suggests that these microparticles can serve as good candidate for oral protein delivery. (c) 2005 Wiley Periodicals, Inc.Item Novel pH responsive polymethacrylic acid-chitosan-polyethylene glycol nanoparticles for oral peptide delivery(JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS, 2006)In present study, novel pH sensitive polymethacrylic acid-chitosan-polyethylene glycol (PCP) nanoparticles were prepared under mild aqueous conditions via polyelectrolyte complexation. Free radical polymerization of methacrylic acid (MAA) was carried out in presence of chitosan (CS) and polyethylene glycol (PEG) using a water-soluble initiator and particles were obtained spontaneously during polymerization without using organic solvents or surfactants/steric stabilizers. Dried particles were analyzed by scanning electron microscopy (SEM) and particles dispersed in phosphate buffer (pH 7.0) were visualized under transmission electron microscope (TEM). SEM studies indicated that PCP particles have an aggregated and irregular morphology, however, TEM revealed that these aggregated particles were composed of smaller fragments with size less than 1 micron. Insulin and bovine serum albumin (BSA) as model proteins were incorporated into the nanoparticles by diffusion filling method and their in vitro release characteristics were evaluated at pH 1.2 and 7.4. PCP nanoparticles exhibited good protein encapsulation efficiency and pH responsive release profile was observed under in vitro conditions. Trypsin inhibitory effect of these PCP nanoparticles was studied using casein substrate and these particles displayed lesser inhibitory effect than reference polymer carbopol. Preliminary investigation suggests that these particles can serve as good candidate for oral peptide delivery. (c) 2005 Wiley Periodicals Inc.Item Poly methacrylic acid-alginate semi-IPN microparticles for oral delivery of insulin: A preliminary investigation(JOURNAL OF BIOMATERIALS APPLICATIONS, 2004) Sajeesh, S; Sharma, CPMicroparticles of Poly methacrylic acid (PI) and novel semi-interpenetrating network composed of Poly methacrylic acid-alginate (P2) were prepared and their application in oral insulin delivery was evaluated. The microparticles were characterized by scanning electron microscopy (SEM) for morphological studies. Insulin loading onto the microparticles was performed by the diffusion filling method and insulin encapsulated microparticles were subjected to in vitro release study in buffer solution of pH 1.2 and 7.4. The release kinetics at pH 7.4 exhibited sustained release of insulin for more than 5 h in case of PMAA microparticles whereas burst release of insulin (90% of total insulin loaded) within 1 h of study was observed in the case of PMAA-alginate microparticles. At pH 1.2, around 30% of insulin loaded was released from both microparticles within 2 h of study.