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Polymer integrity related absorption mechanism of superporous hydrogel containing interpenetrating polymer networks for oral delivery of insulin

Paper ID Volume ID Publish Year Pages File Format Full-Text
8140 578 2010 10 PDF Available
Title
Polymer integrity related absorption mechanism of superporous hydrogel containing interpenetrating polymer networks for oral delivery of insulin
Abstract

Superporous hydrogel containing poly(acrylic acid-co-acrylamide)/O-carboxymethyl chitosan interpenetrating polymer networks (SPH-IPN) was evaluated as the oral delivery vehicle for insulin, emphasizing on the effect of polymer integrity on insulin absorption mechanisms. The integral SPH-IPN (I-SPH-IPN) and powdered SPH-IPN (P-SPH-IPN) exhibited potent and equivalent in vitro enzymatic inhibition capacities, which were attributed to both enzyme incorporation and Ca2+ deprivation. Nevertheless, I-SPH-IPN showed marked superiority to P-SPH-IPN in in vivo enzymatic inhibition. Through reversible opening of epithelial tight junctions, I-SPH-IPN notably enhanced paracellular permeability of insulin in Caco-2 cell monolayers and excised rat intestine by 4.9 and 4.2 folds, respectively, wherein I-SPH-IPN outperformed P-SPH-IPN by 2.5 and 2.3 folds, respectively. Besides, orally delivered I-SPH-IPN could retain in rat intestine for more than 8 h while P-SPH-IPN was quickly eliminated, suggesting better retentive properties of I-SPH-IPN. Such results were further confirmed by in vivo assessment in that oral administration of insulin-loaded I-SPH-IPN yielded notable insulin absorption and hypoglycemic effect, while P-SPH-IPN was ineffective. Finally, an oral acute and sub-acute toxicity study in mice confirmed biocompatibility of SPH-IPN. Therefore, the detailed mechanism assessment confirmed that I-SPH-IPN was an effective and safe peroral carrier for protein drugs.

Keywords
Interpenetrating polymer networks superporous hydrogel; Polymer integrity; Oral protein delivery; Enzymatic inhibition; Insulin absorption; Biocompatibility
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Polymer integrity related absorption mechanism of superporous hydrogel containing interpenetrating polymer networks for oral delivery of insulin
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 31, Issue 12, April 2010, Pages 3347–3356
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering