In vitro evaluation of the potential of thiomers for the nasal administration of Leu-enkephalin

It was the aim of this study to evaluate the potential of thiolated polycarbophil for the nasal administration of Leucine-enkephalin (Leu-enkephalin). The enzymatic degradation of Leu-enkephalin on freshly excised bovine nasal mucosa was analysed qualitatively via thin layer chromatography and quantitatively via high performance liquid chromatography (HPLC). The potential of thiolated polycarbophil gels to provide a sustained release for the therapeutic peptide was investigated via diffusion studies. Permeation studies were performed in Ussing-type diffusion chambers with freshly excised bovine nasal mucosa. Results demonstrated that Leu-enkephalin is mainly degraded by the cleavage of tyrosine from the N-terminus of the peptide. Within one hour more than 63.5 +/- 2% of this therapeutic peptide are degraded on the nasal mucosa. In the presence of 0.25% thiolated polycarbophil, this degradation process, however, could be significantly lowered. Diffusion studies demonstrated that Leu-enkephalin being incorporated in a 0.5% thiolated polycarbophil gel is sustained released out of it. The appearent permeability coefficient (P-app) for Leu-enkephalin on the nasal mucosa was determined to be 1.9 +/- 1.2 x 10(-7) cm/sec. Furthermore, in the presence of 0.5% thiolated polycarbophil and 1% glutathione, which is used as permeation mediator for the thiomer, the uptake of Leu-enkephalin from the nasal mucosa was even 82-fold improved. According to these results thiolated polycarbophil might be a promising excipient for nasal administration of Leu-enkephalin.