Characterization of glucose-mediated insulin release from implantable polymers

Journal of Pharmaceutical Sciences
L R BrownRobert Langer

Abstract

We characterized a glucose-sensitive, controlled-release insulin delivery system. Insulin release rates increased when glucose was perfused in the release media surrounding the matrix. The system was composed of solid, particulate insulin, incorporated into an ethylene-vinyl acetate copolymer (EVAc) matrix. Feedback control was mediated by the glucose oxidase enzyme immobilized to Sepharose beads, which were incorporated along with insulin into the EVAc matrix. When glucose in solution entered the insulin delivery system, gluconic acid was produced, causing a drop in the microenvironmental pH of the matrix. This fall in pH resulted in a rise in insulin solubility and consequently a rise in the insulin release rate from the matrix. Insulin concentrations increased in vitro and in vivo in response to glucose infusion. The increased insulin release was shown to consist of a finite pulse of insulin that required an optimal recovery period of 1 h to achieve a maximal repeated response to a glucose stimulus. Repeated pulses were demonstrated over a 4 h period. An optimum enzyme ratio was also determined.

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Citations

Nov 2, 2001·Journal of Controlled Release : Official Journal of the Controlled Release Society·J J Kim, K Park
Jun 6, 2000·Advanced Drug Delivery Reviews·N J Medlicott, I G Tucker
Jan 27, 1999·Journal of Pharmacological and Toxicological Methods·A K Dash, G C Cudworth
Jun 6, 2002·Drug Discovery Today·Piyush GuptaSanjay Garg
Jun 7, 2008·Journal of Biomaterials Science. Polymer Edition·Tamar TraitelJoseph Kost
Jul 2, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ronald A Siegel
Apr 12, 2002·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kai Zhang, Xiao Yu Wu
Jan 15, 2008·Urologic Oncology·Frank AlexisOmid C Farokhzad
Mar 5, 2003·Journal of Biomaterials Applications·N K Kavitha Raj, Chandra P Sharma
Nov 21, 2013·Advanced Healthcare Materials·Jin DiZhen Gu
Nov 28, 2012·Advanced Healthcare Materials·Kaitlin M BratlieDaniel G Anderson
Jul 11, 2013·Macromolecular Bioscience·Weitai Wu, Shuiqin Zhou
Aug 2, 2018·Anais Da Academia Brasileira De Ciências·Ricardo I CastroLuis Guzmán
Aug 7, 2013·Molecular Pharmaceutics·Beata ChertokRobert Langer

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