(88a) Controlled Release of Type-2 Diabetes Systems

Type-2 diabetes is characterized by insulin-resistance, hyperglycemia, and dysfunctional insulin hormone signaling, and accounts for 90-95% of all total cases of diabetes.⁽¹⁾ The total population affected is expected to reach 4.4% worldwide in 2030.⁽²⁾ Current treatment of type-2 diabetes involves a drug regimen, using small molecule pharmaceutics that act on biological pathways to regulate glycemic control. These drugs modulate glucose metabolism, insulin secretion, and/or insulin sensitivity. Best results are observed with optimal patient compliance. Controlled drug delivery could be leveraged to reduce the dependence on patient compliance and enable more autonomous therapies. Specifically, drug delivery from polymeric biodegradable constructs or stimuli-response "smart" gels provide a basis for self-regulated systems.⁽³⁾  In the context of diabetes therapy, glucose is an especially relevant trigger in the design of polymeric drug delivery systems.⁽⁴⁾  In this work, we have developed several drug-delivery formulations that provide long-term temporal control over drug release. These efforts have resulted in the successful encapsulation of type-2 diabetes drugs, and control over their release kinetics over a period of days. Further efforts to make autonomous therapies will continue to investigate tighter control over glucose-responsive polymeric constructs, with the eventual goal of developing smart glucose-sensing technology for on-demand drug delivery that responds in real time to patient glucose levels. Preliminary efforts have also explored the use of these particles to control blood glucose levels in an animal model of type-2 diabetes. It is our hope that, through this work, the efficacy of type-2 diabetes drug therapy will be improved through smarter design of materials-based therapies.

1. Chronic Disease Prevention and Health Promotion: Diabetes. (2011). Retrieved June 22, 2014, from http://www.cdc.gov/chronicdisease/resources/publications/aag/ddt.htm

2. Wild, S., Roglic, G., Green, A., Sicree, R., King, H. Global Prevalence of Diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care 2004, 27, 1047–1053.

3. Matsumoto, A., Ishii, T., Nishida, J., Matsumoto, H., Kataoka, K., Miyahara, Y. A Synthetic Approach Toward a Self-Regulated Insulin Delivery System. Angew. Chem. Int. Ed. 2012, 51, 2124 –2128

4. Kitano, S., Koyama, Y., Kataoka, K., Okano, T., Sakurai, Y. A novel drug delivery system utilizing a glucose responsive polymer complex between poly (vinyl alcohol) and poly (IV-vinyl-2-pyrrolidone) with a phenylboronic acid moiety. Journal of Controlled Release. 1992, 19, 162–l70.