[New CPEs for transdermal delivery]
>>Published online before print March 17, 2005
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0501176102
Design principles of chemical penetration enhancers for transdermal drug delivery
( stratum corneum | spectroscopy | skin irritation | lipid )
Pankaj Karande *, Amit Jain *, Kaitlin Ergun, Vincent Kispersky, and Samir Mitragotri *
Department of Chemical Engineering, University of California, Santa Barbara, CA 93106
Communicated by Jacob N. Israelachvili, University of California, Santa Barbara, CA, February 11, 2005 (received for review November 18, 2004)
Chemical penetration enhancers (CPEs) are present in a large number of transdermal, dermatological, and cosmetic products to aid dermal absorption of curatives and aesthetics. This wide spectrum of use is based on only a handful of molecules, the majority of which belong to three to four typical chemical functionalities, sporadically introduced as CPEs in the last 50 years. Using >100 CPEs representing several chemical functionalities, we report on the fundamental mechanisms that determine the barrier disruption potential of CPEs and skin safety in their presence. Fourier transform infrared spectroscopy studies revealed that regardless of their chemical make-up, CPEs perturb the skin barrier via extraction or fluidization of lipid bilayers. Irritation response of CPEs, on the other hand, correlated with the denaturation of stratum corneum proteins, making it feasible to use protein conformation changes to map CPE safety in vitro. Most interestingly, the understanding of underlying molecular forces responsible for CPE safety and potency reveals inherent constraints that limit CPE performance. Reengineering this knowledge back into molecular structure, we designed >300 potential CPEs. These molecules were screened in silico and subsequently tested in vitro for molecular delivery. These molecules significantly broaden the repertoire of CPEs that can aid the design of optimized transdermal, dermatological, and cosmetic formulations in the future.<<
Wonder if they'll license or found a company or something.
Cheers, Tuck |
