title: Synthesis and in vitro stability of amino acid prodrugs of 6-β-naltrexol for microneedle-enhanced transdermal delivery.
abstract: A small library of amino acid ester prodrugs of 6-β-naltrexol (NTXOL, 1) was prepared in order to investigate the candidacy of these prodrugs for microneedle-enhanced transdermal delivery. Six amino acid ester prodrugs were synthesized (6a-f). 6b, 6d, and 6 e were stable enough at skin pH (pH 5.0) to move forward to studies in 50% human plasma. The lead compound (6 e) exhibited the most rapid bioconversion to NTXOL in human plasma (t1/2 = 2.2 ± 0.1h).
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA; AllTranz, Lexington, KY 40505, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Eldridge
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: Mikolaj
authors.initials: M
authors.lastname: Milewski
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA; AllTranz, Lexington, KY 40505, USA.
authors.forename: Audra L
authors.initials: AL
authors.lastname: Stinchcomb
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Electronic address: pacrooks@uams.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Crooks
mesh_terms: D000279:Administration, Cutaneous; D000596:Amino Acids / Q000008:administration & dosage / Q000138:chemical synthesis; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D009339:Needles; D011355:Prodrugs / Q000008:administration & dosage* / Q000138:chemical synthesis*; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology
chemical_list: D000596:Amino Acids; D011355:Prodrugs; C010410:6 beta-hydroxynaltrexone; D009271:Naltrexone
keywords: Amino acid esters; Microneedles; Prodrugs; Stability; Transdermal