DESIGN PRINCIPLES OF CHEMICAL PENETRATION ENHANCERS FOR TRANSDERMAL DRUG DELIVERY.

This study by researchers at the University of California at Santa Barbara demonstrated how MatTek’s EpiDerm human skin tissue equivalent can be used to measure the irritation potential of chemical penetration enhancers (CPEs) present in a large number of transdermal, dermatological, and cosmetic products. 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, researchers at the University of California at Santa Barbara (USA) 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. (The irritation potential of CPEs was estimated from the MTT tissue viability assay of normal human-derived epidermal keratinocytes in EpiDerm human skin tissue equivalents). Most interestingly, the understanding of underlying molecular forces responsible for CPE safety and potency reveals inherent constraints that limit CPE performance. Re-engineering this knowledge back into molecular structure, the scientists 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.

CPE, Chemical penetration enhancers (CPE’s), EpiDerm, Irritation potential (IP), MTT, MTT (methyl thiazol tetrazoliym) assay, Porcine epidermis, Skin irritation, Transdermal drug delivery, Zwitterionic, Zwitterionic surfactants

Anionic surfactants (AI), Azone like compounds (AZ), Cationic surfactants (CI), Chemical Penetration Enhancers (CPE), Fatty acids (FA), Fatty amines (FM), Fatty esters (FE), Insulin, Nonionic surfactants (NI), Sodium salts of fatty acids (SS), Zwitterionic surfactants (ZI)