Design of a glucose reponsive, insulin releasing device using polymers containing boronic acid groups

概要

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The purpose of this study was the preparation of a controlled release system for insulin responding to glucose concentrations. Boronic acid groups are known to have the ability to make complexes with molecules having hydroxyl groups. To make hydrogels containing boronic acid groups, methacrylamidephenylboronic acid was co-polymerized with acrylamide, and N, N'-methylenebis(acrylamide). Bovine insulin was hydroxylated with gluconic acid, and the modified insulin was added to the swollen boronic acid beads to make complexes with boronic acid groups. This gel was subsequently packed into chromatography column, and the eluent solutions were alternatively cycled between glucose containing (200 mg/dl) HEPES buffer solution and HEPES buffer solution. Exchange reaction of complexes comprising boronic polymers and hydroxylated insulin with glucose occurred. The concentration of released modified insulin was responsive to the repeated concentration changes of glucose in the eluent. The released amount of modified insulin was 0.38mg/hr.·cm2 in the pulsatile response experiment. This quantity was sufficient for the design of an implantable insulin release system.
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