title: Development of polyether urethane intravaginal rings for the sustained delivery of hydroxychloroquine.
abstract: Hydroxychloroquine (HCQ) has been shown to demonstrate anti-inflammatory properties and direct anti-HIV activity. In this study, we describe for the first time the fabrication and in vitro evaluation of two types of intravaginal ring (IVR) devices (a surfaced-modified matrix IVR and a reservoir segmental IVR) for achieving sustained delivery (>14 days) of HCQ as a strategy for preventing male-to-female transmission of HIV. Both IVRs were fabricated by hot-melt injection molding. Surface-modified matrix IVRs with polyvinylpyrrolidone or poly(vinyl alcohol) coatings exhibited significantly reduced burst release on the first day (6.45% and 15.72% reduction, respectively). Reservoir IVR segments designed to release lower amounts of HCQ displayed near-zero-order release kinetics with an average release rate of 28.38 μg/mL per day for IVRs loaded with aqueous HCQ and 32.23 μg/mL per day for IVRs loaded with HCQ mixed with a rate-controlling excipient. Stability studies demonstrated that HCQ was stable in coated or noncoated IVRs for 30 days. The IVR segments had no significant effect on cell viability, pro-inflammatory cytokine production, or colony formation of vaginal and ectocervical epithelial cells. Both IVR systems may be suitable for the prevention of HIV transmission and other sexually transmitted infections.
authors.affiliation: Laboratory for Drug Delivery and Biomaterials, Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Laboratory for Drug Delivery and Biomaterials, Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Yannick Leandre
authors.initials: YL
authors.lastname: Traore
authors.affiliation: Laboratory for Drug Delivery and Biomaterials, Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Amanda
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada ; Department of Community Health Sciences, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fowke
authors.affiliation: Laboratory for Drug Delivery and Biomaterials, Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Ho
mesh_terms: D000282:Administration, Intravaginal; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004355:Drug Stability; D006801:Humans; D006886:Hydroxychloroquine / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D011140:Polyurethanes / Q000138:chemical synthesis / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D011140:Polyurethanes; C115016:polyetherurethane; D006886:Hydroxychloroquine
keywords: HIV/AIDS; drug release; intravaginal delivery; matrix system; microbicide; polymeric drug carrier; reservoir system