Characterization of model solute and insulin delivery across covalently modified lectin-polysaccharide gels sensitive to glucose

Abstract

An in-vitro self-regulating drug delivery system is described which uses a glucose-sensitive gel based on concanavalin A (Con A) and a polysaccharide displacement mechanism. Con A was covalently coupled with dextran to address the problem of significant leaching of the mitogenic lectin as encountered previously. This was accomplished using periodate-induced Schiff's bases. The resulting gels, like the uncoupled gels, were shown to undergo a gel-sol transformation in response to glucose. Gels formulated in this way were examined for Con A retention and for glucose responsiveness in terms of differential delivery of a model solute tartrazine and insulin. Initial studies at 20°C revealed that the efficacy of the covalent coupling was influenced by dextran molecular weight and concentration, Con A concentration and Con A solution pH. All formulations studied restricted Con A escape significantly with respect to non-coupled gels. The delivery of insulin was demonstrated using this covalently modified gel system in conditions of repeated glucose triggering at 20°C and 37°C. A dose-related magnitude of the glucose response was apparent. The performance of this self-regulating system has been improved in terms of reduced Con A leaching. This study demonstrated the feasibility of delivering insulin in a self-regulating drug delivery system.