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.
Bernkop-Schnürch
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A
Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold Franzens University Innsbruck, Innsbruck, Austria. andreas.bernkop@uibk.ac.at
Obermair
K
K
Greimel
A
A
Palmberger
T F
TF
D000180:Acrylic Resins / Q000737:chemistry / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002417:Cattle; D004353:Drug Evaluation, Preclinical; D004743:Enkephalin, Leucine / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013997:Time Factors
D000180:Acrylic Resins; D005079:Excipients; D013438:Sulfhydryl Compounds; D004743:Enkephalin, Leucine; C030312:calcium polycarbophil