In Vivo Analysis of Insulin Delivery Using CPEs Designed Via In Silico QSPR Approach

The uneasiness and pain of multiple injection therapy courses for diabetic patients and the non-compliance of patients with poorly controlled type 2 diabetes have prompted the development of alternative, pain-free delivery methods.  Transdermal drug delivery is gaining significance in the recent years due to its advantages over other invasive methods.  An insulin transdermal patch placed on the skin may be able to deliver sustained physiological levels of basal insulin in a pain-free manner; however, since insulin is a relatively large molecule, it does not penetrate the skin easily.  Altering the characteristics of the skin by using chemicals called penetration enhancers is one of the promising ways to breach the skin’s barrier to drugs.  Using this concept, we have reported on the methodology of predicting CPEs using improved algorithms for non-linear, quantitative structure-property relationship (QSPR) models based upon representative molecular properties [1-7].  The predicted molecules were extensively tested for cytotoxicity and ex vivo delivery.  This study focuses in evaluating the in vivo efficacy delivering insulin across the skin with and without CPEs in a rodent model.  Rats were starved eight hours before the application of the patch and then blood glucose levels were monitored.  After five days, we evaluated the overall body weight change, hepatotoxicity and skin toxicity.  Our findings through animal trials indicate proven efficacy of the newly designed CPEs.