期刊
ACTA BIOMATERIALIA
卷 6, 期 8, 页码 3072-3080出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2010.02.007
关键词
Oral insulin; Hydrogel; Microparticles; Thiolation; Mucoadhesion
资金
- Department of Science and Technology, New Delhi
- French Embassy in India
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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