Session Speaker

Virtual Design of Chemical Penetration Enhancers for Transdermal Drug Delivery of Insulin
B. J. Neely; K. M. Yerramsetty; E. A. Whitebay; V. K. Rachakonda, S. Golla; J. D. Ramsey; H. D. N. Fahlenkamp, S. V. Madihally,R. L. Robinson, Jr. K. A. M. Gasem
USA

Carefully designed chemical penetration enhancers (CPEs) offer significant opportunities for transdermal drug delivery (TDD). However, discovering effective CPEs using traditional drug design is a laborious and expensive process that often challenges pharmaceutical industries. Further, delivery of proteins such as insulin is problematic due to molecular size and structural attributes. As a result, researchers have turned to the computational methods of computer-aided molecular design.

Recently, we have demonstrated that (a) genetic and evolutionary algorithms are capable of addressing the combinatorial problems associated with computer-aided molecular design of CPEs, and (b) combining genetic algorithms (GAs) with non-linear quantitative structure-property relationship (QSPR) analyses provides a reliable virtual screening algorithm for generation of potential CPEs.

Our GA-QSPR virtual design methodology has been implemented successfully to identify potential CPEs for transdermal drug delivery of insulin. Validation of the newly identified CPE molecular structures was conducted through carefully designed in vitro experiments, which elucidated the cytotoxicity and permeability of the CPEs. The virtual design produced 19 CPE candidates, and after experimental validation, eight CPEs were discovered that were both highly enhancing (permeability coefficient at least four times larger than control) and non-toxic. Three of these were investigated previously in the literature, and five are novel discoveries