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
A. Ruland et al., 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, International journal of pharmaceutics, 107(1), 1994, pp. 23-28
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.