Super long-term glycemic control in diabetic rats by glucose-sensitive LbL films constructed of supramolecular insulin assembly.

Abstract

The supramolecular assembly of porcine insulin (P-SIA) is prepared at moderate condition and monitored by Thioflavin T fluorescence to avoid the formation of mature amyloid fibrils with β-sheet rich structure. P-SIA is characterized in terms of structure, morphology and the capability of sustained insulin release in vitro. Then, a glucose-sensitive layer-by-layer (LbL) film is fabricated with star poly[2-(dimethylamino)ethyl methacrylate] (star-PDMAEMA), glucose oxidase (GOD), catalase (CAT) and P-SIA in the form of {(Star-PDMAEMA/P-SIA)(2) + (Star-PDMAEMA/CAT)(1) + (Star-PDMAEMA/GOD)(2)}(2) + Star-PDMAEMA, in which the CAT is introduced to eliminate the aggregated H(2)O(2) and maintain the activity of GOD in the long release time. Within the scope of the investigation, a single dose administration could provide effective glycemic control in diabetic rats for up to 295 days without hypoglycemia. The striking result is contributed both by the inherent property of P-SIA and the glucose-sensitive regulation capability of the LbL film, for which the mechanism was thoroughly investigated both in vitro and in vivo. These findings are valuable to inspire more researches to combine supramolecular insulin assembly with various functional drug delivery systems, biochemical additives, biomaterials and biomedical devices for diabetic therapy.