title: Evaluation of polycaprolactone matrices for the intravaginal delivery of metronidazole in the treatment of bacterial vaginosis.
abstract: Microporous, poly (ɛ-caprolactone) (PCL) matrices loaded with the antibacterial, metronidazole were produced by rapidly cooling suspensions of drug powder in PCL solutions in acetone. Drug incorporation in the matrices increased from 2.0% to 10.6% w/w on raising the drug loading of the PCL solution from 5% to 20% w/w measured with respect to the PCL content. Drug loading efficiencies of 40-53% were obtained. Rapid 'burst release' of 35-55% of the metronidazole content was recorded over 24 h when matrices were immersed in simulated vaginal fluid (SVF), due to the presence of large amounts of drug on matrix surface as revealed by Raman microscopy. Gradual release of around 80% of the drug content occurred over the following 12 days. Metronidazole released from PCL matrices in SVF retained antimicrobial activity against Gardnerella vaginalis in vitro at levels up to 97% compared to the free drug. Basic modelling predicted that the concentrations of metronidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration of metronidazole against G. vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of metronidazole in the treatment and prevention of bacterial vaginosis.
authors.affiliation: The University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Pathak
authors.affiliation: The University of Queensland, School of Agriculture and Food Sciences, St. Lucia, Queensland, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Turner
authors.affiliation: Princess Alexandra Hospital, Dept. of Sexual health, Queensland, Australia.
authors.forename: Cheryn
authors.initials: C
authors.lastname: Palmer
authors.affiliation: The University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, Brisbane, Queensland, Australia The International Medical University, School of Pharmacy, Bukit Jalil, Kuala Lumpur, Malaysia AllanCoombes@imu.edu.my.
authors.forename: Allan G A
authors.initials: AG
authors.lastname: Coombes
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008795:Metronidazole / Q000008:administration & dosage* / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D011091:Polyesters / Q000008:administration & dosage*; D013059:Spectrum Analysis, Raman; D014621:Vagina; D016585:Vaginosis, Bacterial / Q000188:drug therapy*
chemical_list: D000890:Anti-Infective Agents; D004337:Drug Carriers; D011091:Polyesters; D008795:Metronidazole; C016240:polycaprolactone
keywords: Bacterial vaginosis; intravaginal rings; metronidazole; polycaprolactone