Dermal peptide delivery using enhancer moleculs and colloidal carrier systems. Part II: Tetrapeptide PKEK.

Due to the lipophilic properties of the uppermost skin layer of the stratum corneum (SC) it is highly challenging to reach therapeutic concentrations of cosmetic actives and drugs. Particularly, the hydrophilic ones penetrate poorly across the SC. The purpose of this study was to improve the topical bioavailability of the hydrophilic, polar tetrapeptide PKEK (amino acid sequence in one-letter notation). A nano-sized carrier system (microemulsion, ME) was therefore developed since MEs provide excellent penetration enhancing properties. The penetration of PKEK from the ME was compared to the penetration from a standard formulation. For the two preparations the penetration of the tetrapeptide in ex vivo human skin was investigated. This allows to make statements 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 incorporation of PKEK into a ME system. Relatively high amounts between 40 and 58% of the tetrapeptide PKEK penetrated from the standard cream into the skin. The major proportion of PKEK, which penetrated from the standard cream, remained in the SC and did not reach the target compartment within the skin. Penetration of PKEK from the ME was comparable with the cream for the shortest test time. However, very high PKEK amounts penetrated form the nano-sized carrier system (ME) into the human skin after 100 min (94%) and after 300 min (88%). The largest proportion did not remain in the skin, but permeated into the acceptor compartment. Therefore, the relative peptide content in the viable skin layers was predominantly comparable for the cream and the ME. For some samples a tendency could be observed that slightly higher amounts of PKEK were detected after the application of the standard cream. The absolute peptide concentrations gave a similar conclusion. The results indicate that liquid nano-sized systems are very effective carriers for extremely hydrophilic peptides used in cosmetics and also in therapeutics.