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Title: Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery
Authors: Sajeesh, S.
Vauthier, C.
Gueutin, C.
Ponchel, G.
Sharma, Chandra P.
Keywords: Drug Delivery
Issue Date: 2010
Citation: ACTA BIOMATERIALIA. 6; 8; 3072-3080
Abstract: 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
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