Permeation of a myristoylated dipeptide across the buccal mucosa: topological distribution and evaluation of tissue integrity.
The ex vivo permeation of an acylated model dipeptide, Myristoyl-Tryptophan-Leucine (Myr-Trp-Leu) was studied using pig buccal mucosa. Myr-Trp-Leu, being lipophilic, did not readily penetrate across the membrane. Rather, it accumulated in the epithelial and connective tissue of the mucosal barrier. The topological distribution of Myr-Trp-Leu across the mucosa, following its application in ethanol/phosphate buffer (30/70 pH 7.4), was determinated by thin-sectioning of the tissue, extraction of the peptide, and high performance thin layer chromatography (HPTLC). The concentration profile depended, of course, on the duration of the experiment and appeared to be dependent upon the presence of sufficient ethanol in order that the peptide could be solubilized. This important role for ethanol then raised the question of the solvent's effect on tissue integrity. Light microscopic examination of the mucosa was, therefore, undertaken, under identical conditions to those used in the permeation experiments, to evaluate any perturbation induced by the ethanolic vehicle. No obvious effects were observed.
Veuillez
F
F
Pharmapeptides, Centre interuniversitaire de recherche et d'enseignement, 74166, Archamps, France.
Rieg
F Falson
FF
Guy
R H
RH
Deshusses
J
J
Buri
P
P
D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics; D004151:Dipeptides / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000431:Ethanol / Q000493:pharmacokinetics; D007930:Leucine / Q000493:pharmacokinetics; D009061:Mouth Mucosa / Q000378:metabolism*; D019814:Myristic Acid / Q000493:pharmacokinetics*; D013552:Swine; D014018:Tissue Distribution; D014364:Tryptophan / Q000493:pharmacokinetics
D002492:Central Nervous System Depressants; D004151:Dipeptides; D019814:Myristic Acid; D000431:Ethanol; D014364:Tryptophan; D007930:Leucine