title: Evaluation of polycaprolactone matrices for sustained vaginal delivery of nevirapine in the prevention of heterosexual HIV transmission.
abstract: Nevirapine (NVP) was loaded in polycaprolactone (PCL) matrices to produce vaginal inserts with the aim of preventing HIV transmission. NVP dispersions in PCL were prepared, at 10% (w/w) theoretical loading, measured with respect to the PCL content of the matrices, in the form of (1) NVP only, (2) a physical mixture of NVP with polyethylene glycol (PEG) 6000 or (c) a solid dispersion (SD) with PEG produced by co-dissolution in ethanol. Characterisation of SD by differential scanning calorimetry and attenuated total reflectance-Fourier transform infrared spectroscopy suggested transformation of the crystalline structure of NVP to an amorphous form which consequently increased the dissolution rate of drug. A low-loading efficiency of 13% was obtained for NVP-loaded matrices and less than 20% for matrices prepared using physical mixtures of drug and PEG. The loading efficiency was improved significantly to around 40% when a 1:4 NVP-PEG SD was used for matrix production. After 30 days, 40% of the drug content was released from NVP-loaded matrices, 55% from matrices containing 1:4 NVP-PEG physical mixtures and 60% from matrices loaded with 1:4 NVP-PEG SDs. The in vitro anti-viral activity of released NVP was assessed using a luciferase reporter gene assay following the infection of HeLa cells with pseudo-typed HIV-1. NVP released from PCL matrices in simulated vaginal fluid retained over 75% anti-HIV activity compared with the non-formulated NVP control. In conclusion, 1:4 NVP-PEG SDs when loaded in PCL matrices increase drug loading efficiency and improve release behaviour.
authors.affiliation: School of Pharmacy, The University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: Nhung
authors.initials: N
authors.lastname: Dang
authors.affiliation: Queensland Institute of Medical Research, Molecular Virology Laboratory, Brisbane, Queensland 4811, Australia.
authors.forename: Haran
authors.initials: H
authors.lastname: Sivakumaran
authors.affiliation: Queensland Institute of Medical Research, Molecular Virology Laboratory, Brisbane, Queensland 4811, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Harrich
authors.affiliation: School of Pharmacy, The University of Queensland, St. Lucia, Queensland 4072, Australia.
authors.forename: P Nicholas
authors.initials: PN
authors.lastname: Shaw
authors.affiliation: School of Pharmacy, The University of Queensland, St. Lucia, Queensland 4072, Australia. Electronic address: AllanCoombes@imu.edu.my.
authors.forename: Allan G A
authors.initials: AGA
authors.lastname: Coombes
mesh_terms: D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D018562:Disease Transmission, Infectious / Q000517:prevention & control*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission*; D015497:HIV-1 / Q000187:drug effects; D006367:HeLa Cells; D020010:Heterosexuality; D006801:Humans; D020128:Inhibitory Concentration 50; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use*; D011091:Polyesters / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties
chemical_list: D019380:Anti-HIV Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; C016240:polycaprolactone; D019829:Nevirapine
keywords: biomaterial; controlled release; drug delivery systems; microbicides; nevirapine; polycaprolactone matrix; solid dispersion; vaginal delivery