Characterization of glucose-dependent gel-sol phase transition of the polymeric glucose-concanavalin A hydrogel system
Abstract
Development of modulated insulin delivery devices is important for the control of diabetes because simple replacement of insulin by periodic injections is unable to prevent complications resulting from this disorder. Polymeric hydrogels have been studied extensively as potential devices to control the release of insulin. An ideal insulin delivery system would have the capability to sense the glucose level in the blood and release the appropriate amount of insulin. The main goal of this study was to synthesize and characterize hydrogels which undergo reversible gel-sol phase transformation in response to changes in glucose concentration in the surrounding environment. The glucose-sensitive hydrogels were made by mixing the appropriate concentrations of acrylamide-allyl glucose copolymer and concanavalin A (Con A). The efficacy of hydrogel formation increased as the copolymer concentration decreased at a fixed concentration of Con A. To examine their phase reversibility, hydrogels in dialysis membranes were cycled between glucose-free and glucose-containing buffers. The synthesized hydrogels underwent phase transition to sol in the presence of free glucose in the surrounding environment. The non-covalent crosslinking of glucose-containing polymer chains through Con A provides the gel-sol phase reversibility. The concentration of external free glucose had to be at least 4 times that of polymer-bound glucose to induce phase transition from gel to sol. Cooperative interactions between polymer-bound glucose and Con A were observed when the concentration of polymer-bound glucose in the gel was increased to 0.42 mg/ml. Above the concentration, external free glucose had to be much higher than 4 times that of polymer-bound glucose to induce phase transition to sol. The binding affinity study showed that binding of allyl glucose to Con A was 4 times stronger than that of free glucose to Con A. The non-linear dependence of phase transition was explained by the increased binding affinity of allyl glucose over native glucose to Con A, and the cooperative interactions between polymer-bound glucose and Con A. The hydrogel membranes were found to control the release of proteins, such as insulin and lysozyme, in response to the changing concentration of free glucose.
Degree
Ph.D.
Advisors
Park, Purdue University.
Subject Area
Pharmaceuticals
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