(126d) Screening Of Chemical Penetration Enhancers For Transdermal Drug Delivery

Transdermal drug delivery is gaining importance in the recent years due to its advantages over other traditional methods. 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. However, identifying potential enhancers for a specific drug is both difficult and time consuming. This study describes a novel technique for screening chemical penetration enhancers (CPEs) using impedance measurements.

Changes in the permeation of the skin can be assessed through its conductive properties, as given by frequent impedance measurements performed over a 24-hour period. In this study, measurements were conducted using a newly-constructed impendence chamber, which was designed to measure skin impendence at three different chemical concentrations simultaneously. The apparatus was optimized to minimize the effects of skin dehydration, and improve its reproducibility. The unit was calibrated using polymeric chitosan membranes and commercially available conductive fabrics (800 Ω/sq. range).

The experimental setup was validated using CPEs reported in the literature on porcine skin in vitro. Further, tests were performed to validate the chemical enhancers generated by virtual screening algorithms that integrated non-linear QSPR models and genetic algorithms [1, 2]. Preliminary results from the impedance technique show good reproducibility and appear promising in characterizing skin penetration potential.

The chemical enhancers are additionally tested for their toxicity on Mouse Embryonic Fibroblasts (MEFs) with MTT assay at the end of a 24-hour exposure period to the chemicals. Nearly 20 chemicals were tested at two different concentrations. 40% of the CPEs examined were found to be non-toxic at the highest concentrations used.

References

1. E. A. Whitebay, S. Golla, B. J. Neely, S. V. Madihally, R. L. Robinson Jr., and K. A. M. Gasem, Developing New Models to Predict Drug Properties, submitted to 2007 AIChE Annual Meeting, Salt Lake City, Utah

2. S. Golla, E. A. Whitebay, B. J. Neely, S. V. Madihally, R. L. Robinson Jr., and K. A. M. Gasem, A Genetic Algorithm for Virtual Design of Chemical Penetration Enhancers, submitted to 2007 AIChE Annual Meeting, Salt Lake City, Utah