title: Diffusion of naltrexone across reconstituted human oral epithelium and histomorphological features.
abstract: In transbuccal absorption a major limitation could be the low permeability of the mucosa which implies low drug bioavailability. The ability of naltrexone hydrochloride (NLX) to penetrate a resembling histologically human buccal mucosa was assessed and the occurrence of any histomorphological changes observed. We used reconstituted human oral (RHO) non-keratinised epithelium as mucosal section and a Transwell diffusion cells system as bicompartmental model. Buccal permeation was expressed in terms of drug flux (J(s)) and permeability coefficients (K(p)). Data were collected using both artificial and natural human saliva. The main finding was that RHO does not restrain NLX permeation. Drug transport across the epithelium was observed also in presence of various concentrations of penetration enhancers, without any significant differences. On the contrary, the flux throughout the mucosa was extensively affected by iontophoresis. Histologically, no sign of flogosis was observed in any specimen under experiment without iontophoresis, whereas cytoarchitectural changes, up to nuclear pycnosis or cellular swelling, were determined as a consequence of the application of electric fields.
authors.affiliation: Dipartimento di Chimica e Tecnologie Farmaceutiche, Università di Palermo, Via Archirafi 32, 90123 Palermo, Italy. litagian@unipa.it
authors.forename: Libero Italo
authors.initials: LI
authors.lastname: Giannola
authors.forename: Viviana
authors.initials: V
authors.lastname: De Caro
authors.forename: Giulia
authors.initials: G
authors.lastname: Giandalia
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Siragusa
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Campisi
authors.forename: Ada Maria
authors.initials: AM
authors.lastname: Florena
authors.forename: Tomasz
authors.initials: T
authors.lastname: Ciach
mesh_terms: D000042:Absorption; D000278:Administration, Buccal; D002470:Cell Survival; D003627:Data Interpretation, Statistical; D004058:Diffusion; D004558:Electric Stimulation; D004848:Epithelium / Q000378:metabolism; D005079:Excipients / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007478:Iontophoresis; D009061:Mouth Mucosa / Q000033:anatomy & histology / Q000378:metabolism*; D009271:Naltrexone / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D016612:Paraffin Embedding; D010539:Permeability; D016707:Tissue Fixation
chemical_list: D005079:Excipients; D009292:Narcotic Antagonists; D009271:Naltrexone