COMPARISON OF THE EX-VIVO ORAL MUCOSAL PERMEATION OF TRYPTOPHAN-LEUCINE (TRP-LEU) AND ITS MYRISTOYL DERIVATIVE

The ex vivo permeation of a model peptide, tryptophan-leucine (Trp-Leu ), was studied using two different regions of pig oral mucosa, the har d palate and the cheek. In order to increase the mucosal absorption of Trp-Leu, a lipophilic derivative was synthesized by acylation of the N-terminal amino group of Trp-Leu with myristic acid. The purified Trp -Leu derivative (Myr-Trp-Leu) was more lipophilic than the parent Trp- Leu as observed by HPTLC (R-f's values of 0.41 and 0.81, respectively) . Measurement of partition coefficients in n-octanol/phosphate buffer pH 7.4, gave K-p values of - 0.68 and 1.04 for Trp-Leu and Myr-Trp-Leu , respectively. The native Trp-Leu was unable to pass through the kera tinized layer of palatal mucosa, and after 24 h only 12% had passed th rough the buccal mucosa to the receptor compartment. The higher lipoph ilicity of the acylated peptide, meant that it was not easily transpor ted across the oral mucosal barrier but accumulated in the tissue, fou nding 25 and 70% of the original amount in the palatal and buccal muco sae, respectively. Both, Trp-Leu and Myr-Trp-Leu were found to be stab le in palatal and buccal mucosae. (C) 1998 Elsevier Science B.V. All r ights reserved.