title: Metabolism and absorption enhancement of methionine enkephalin in human nasal epithelium.
abstract: The objective of this study was to investigate absorption enhancing approaches for systemic delivery of methionine enkephalin via the nose. Absorption promotion of methionine enkephalin in the presence of protease inhibitors (bestatin, puromycin) and absorption enhancers (glycocholate, dimethyl-beta-cyclodextrin) were investigated in human nasal epithelium. Co-administration of the peptide with protease inhibitors and absorption enhancers resulted in a remarkable increase in Met-Enk permeation (4- to 94-fold). The increase was proportional to transepithelial resistance reduction and permeation of paracellular marker dye. Perturbation of the epithelial tight junctions seen in vitro may not occur in vivo due to mucus protection and mucociliary clearance.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Health Sciences Building, 900 S. Limestone Street, Room 461, Lexington, KY 40536-0200, USA.
authors.forename: Remigius U
authors.initials: RU
authors.lastname: Agu
authors.forename: H
authors.initials: H
authors.lastname: Vu Dang
authors.forename: Mark
authors.initials: M
authors.lastname: Jorissen
authors.forename: Renaat
authors.initials: R
authors.lastname: Kinget
authors.forename: Norbert
authors.initials: N
authors.lastname: Verbeke
mesh_terms: D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002923:Cilia; D003912:Dextrins / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000493:pharmacokinetics* / Q000494:pharmacology; D006000:Glycocholic Acid / Q000494:pharmacology; D006801:Humans; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology
chemical_list: D003912:Dextrins; D011480:Protease Inhibitors; D011691:Puromycin; D004744:Enkephalin, Methionine; D006000:Glycocholic Acid; D007930:Leucine; C012211:ubenimex