Due to the lipophilic properties of the uppermost skin layer of the stratum corneum (SC), it is highly challenging to attain therapeutic concentrations of active substances; hydrophilic drugs, in particular, penetrate poorly. The purpose of this study was the improvement of the topical bioavailability of the hydrophilic dipeptides L-carnosine and its related compound N-acetyl-L-carnosine. Different strategies were investigated. On the one hand, an enhancer molecule, 1,2-pentylene glycol (PG), was added to a standard preparation, and on the other hand, a microemulsion (ME-PG) system was developed. Both were compared to the standard formulation without an enhancer molecule. For all 3 preparations, the penetration of the peptides in ex vivo human skin was investigated. This allows statements to be made regarding dermal penetration, localization and distribution of the active substances in each skin layer as well as the influence of vehicle variations, in this case, the addition of PG or the incorporation of N-acetyl-L-carnosine in an ME-PG system. For L-carnosine and N-acetyl-L-carnosine, the use of the standard preparation with PG resulted in a significant increase of the substance within the SC. Approximately 6-fold and higher dipeptide concentrations in the SC and in the viable skin layers were detected at all experimental periods compared to the formulation without the enhancer molecule and the ME-PG. High concentrations of the compounds were found after a short period of time in the viable skin layers after applying the enhancer molecule, even in concentrations of 5%. The application of the colloidal carrier system did not lead to a higher penetration rate of N-acetyl-L-carnosine in comparison to both standard preparations, although it must be said that the microstructure of the investigated ME-PG might not have been optimal for the hydrophilic properties of the dipeptide.
Copyright © 2012 S. Karger AG, Basel.