Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery
No Thumbnail Available
Date
2010
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ACTA BIOMATERIALIA
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
Description
Keywords
Drug Delivery
Citation
ACTA BIOMATERIALIA. 6; 8; 3072-3080