TRANSDERMAL DELIVERY OF THE TETRAPEPTIDE HISETAL (MELANOTROPIN(6-9)) AND AMINO-ACIDS - THEIR CONTRIBUTION TO THE ELUCIDATION OF THE EXISTENCE OF AN AQUEOUS PORE PATHWAY

In order to address the problem of the elucidation of overall valid tr ansdermal transport mechanisms, the permeation data on 20 amino acids and on the tetrapeptide hisetal as well as other literature data about skin permeation were analyzed in the present study. In addition, the iontophoretic as well as passive transport of the tetrapeptide hisetal across human skin was studied using Franz cells. The anode was placed in the side of the diffusion cell facing the epidermis and the cathod e in the acceptor compartment. Current densities of 0.5 and 1 mA were applied. After 12 h of passive permeation maximally 1.2 mu g hisetal w as found in the acceptor compartment. After 2 h of iontophoretic deliv ery applying a constant current of 0.5 mA, 18.8 mu g hisetal was detec ted while the application of a constant current of 1 mA for 2 h result ed in 28.7 mu g hisetal in the acceptor compartment. Consequently, ion tophoretic treatment increased the permeation rate of hisetal by a fac tor of 30. In comparison to the use of enhancers, iontophoretic treatm ent is much more effective. Facilitated permeation by enhancer treatme nt increased the permeation rate of hisetal across human skin maximall y by a factor of 6. The results of the analysis of literature data, of our previous work on amino acids and the tetrapeptide hisetal, and of the present iontophoretic study show that the skin does not act as a simple lipoid barrier. The observation that increasing hydrophobicity did not correlate with increasing permeability of these amino acids as well as the finding that no relationship between the molecular weight s of the amino acids and the peptide was observable led to the conclus ion that amino acids and peptides appear to use another pathway throug h the skin. These findings and the fact that iontophoretic treatment i s much more effective than enhancer treatment clearly seem to indicate that amino acids and the peptide permeate the skin mainly through wat er filled pores.