title: Transdermal delivery of naltrexol and skin permeability lifetime after microneedle treatment in hairless guinea pigs.
abstract: Controlled-release delivery of 6-beta-naltrexol (NTXOL), the major active metabolite of naltrexone, via a transdermal patch is desirable for treatment of alcoholism. Unfortunately, NTXOL does not diffuse across skin at a therapeutic rate. Therefore, the focus of this study was to evaluate microneedle (MN) skin permeation enhancement of NTXOL's hydrochloride salt in hairless guinea pigs. Specifically, these studies were designed to determine the lifetime of MN-created aqueous pore pathways. MN pore lifetime was estimated by pharmacokinetic evaluation, transepidermal water loss (TEWL) and visualization of MN-treated skin pore diameters using light microscopy. A 3.6-fold enhancement in steady-state plasma concentration was observed in vivo with MN treated skin with NTXOL.HCl, as compared to NTXOL base. TEWL measurements and microscopic evaluation of stained MN-treated guinea pig skin indicated the presence of pores, suggesting a feasible nonlipid bilayer pathway for enhanced transdermal delivery. Overall, MN-assisted transdermal delivery appears viable for at least 48 h after MN-application.
authors.affiliation: Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky 40536-0082, USA.
authors.forename: Stan L
authors.initials: SL
authors.lastname: Banks
authors.forename: Raghotham R
authors.initials: RR
authors.lastname: Pinninti
authors.forename: Harvinder S
authors.initials: HS
authors.lastname: Gill
authors.forename: Kalpana S
authors.initials: KS
authors.lastname: Paudel
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Brogden
authors.forename: Mark R
authors.initials: MR
authors.lastname: Prausnitz
authors.forename: Audra L
authors.initials: AL
authors.lastname: Stinchcomb
mesh_terms: D000279:Administration, Cutaneous; D000437:Alcoholism / Q000188:drug therapy; D000818:Animals; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
chemical_list: C010410:6 beta-hydroxynaltrexone; D009271:Naltrexone