Insulin is a life saving treatment for millions of diabetics, but it suffers from two major problems. The first of these is that it is not orally bioavailable. Because of this it has to be injected by syringe, thus burdening insulin users with a lifetime of multiple daily injections. The alternative is for it to be delivered by pump and cannul. This creates a physical connection between the patient and the device, which is then subject to clogging, snagging, and crimping. The second major problem with insulin is that it is required in widely varying amounts depending on the patient's blood sugar level. Mismatches lead to high or low blood sugar and compromised patient health. In this proposed work, we propose a new way of delivering insulin that addresses and solves both of these problems: An insulin photoactivated depot. An insulin photoactivated depot consists of insulin linked to an insoluble polymer by a light cleaved linker. The material is intended to be injected just under the skin where it remains, inert, until transdermal irradiation releases insulin. An insulin photoactivated depot could contain many days worth of insulin, and therefore eliminate most of the injections associated with insulin use, while avoiding the physical limitations of a pump. In addition it woul allow for the release of insulin to be varied minute by minute, by varying the duration and intensity of illumination of the depot, and thus permit tight control of blood sugar.
Our specific aims are therefore to 1) Synthesize multiple photoactivated insulin depot materials, based on a wide range of biodegradable polymers. 2) Characterize these depot materials in in vitro settings, determining insulin loading, and efficiency of release with illumination and 3) Assess the ability of the depot materials to effectively release insulin and reduce blood sugar in a diabetic rat model, in response to transdermal illumination. The successful completion of these aims will establish a new approach for the treatment of diabetics, one that greatly improves quality of life by untethering the patient, limiting injections, and allowing for the tight control of blood sugar.
We propose to develop a minimally invasive method for administering insulin in diabetics. This method has the potential to transform the lives of diabetics, by eliminating the physical connection of the insulin delivery device with the patient while improving the control of blood sugar.
| Nadendla, Karthik; Friedman, Simon H (2017) Light Control of Protein Solubility Through Isoelectric Point Modulation. J Am Chem Soc 139:17861-17869 |
| Sarode, Bhagyesh R; Jain, Piyush K; Friedman, Simon H (2016) Polymerizing Insulin with Photocleavable Linkers to Make Light-Sensitive Macropolymer Depot Materials. Macromol Biosci 16:1138-46 |
| Sarode, Bhagyesh R; Kover, Karen; Tong, Pei Y et al. (2016) Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot. Mol Pharm 13:3835-3841 |
