Abstract

The objective of this study is to utilize the pH sensitivity of modified carboxymethyl starch (CMS) for oral delivery of insulin. The chemical modification of natural polymers by grafting has received considerable attention in recent years because of the wide variety of monomers available. Methacrylic-type polymeric prodrugs were synthesized by free radical copolymerization of methacrylic acid, poly(ethyleneglycol monomethyl ether methacrylate) (PEGMA), and carboxymethyl starch (CMS) in the presence of bis-acrylamide as a cross-linking agent (CA) and persulfate as an initiator. The pH sensitive nature and ability to control gel permeability indicate that these materials have significant potential for drug delivery applications. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). Insulin was entrapped in these gels, and the in vitro release profiles were established separately in both (SGF, pH 1) and (SIF, pH 7.4). Drug release studies showed that the increasing content of MAA in the copolymer enhances hydrolysis in SIF. In these cases, the biological activity of insulin was retained. These results were used to design and improve protein release behavior from these carriers.

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