title: Impact of Hydroxychloroquine-Loaded Polyurethane Intravaginal Rings on Lactobacilli.
abstract: The use of polymeric devices for controlled sustained delivery of drugs is a promising approach for the prevention of HIV-1 infection. Unfortunately, certain microbicides, when topically applied vaginally, may be cytotoxic to vaginal epithelial cells and the protective microflora present within the female genital tract. In this study, we evaluated the impact of hydroxychloroquine (HCQ)-loaded, reservoir-type, polyurethane intravaginal rings (IVRs) on the growth of Lactobacillus crispatus and Lactobacillus jensenii and on the viability of vaginal and ectocervical epithelial cells. The IVRs were fabricated using hot-melt injection molding and were capable of providing controlled release of HCQ for 24 days, with mean daily release rates of 17.01 ± 3.6 μg/ml in sodium acetate buffer (pH 4) and 29.45 ± 4.84 μg/ml in MRS broth (pH 6.2). Drug-free IVRs and the released HCQ had no significant effects on bacterial growth or the viability of vaginal or ectocervical epithelial cells. Furthermore, there was no significant impact on the integrity of vaginal epithelial cell monolayers, in comparison with controls, as measured by transepithelial electrical resistance. Overall, this is the first study to evaluate the effects of HCQ-loaded IVRs on the growth of vaginal flora and the integrity of vaginal epithelial cell monolayers.
authors.affiliation: Laboratory for Drug Delivery and Biomaterials, College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Yannick Leandre
authors.initials: YL
authors.lastname: Traore
authors.affiliation: Laboratory for Drug Delivery and Biomaterials, College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biological Sciences, Faculty of Science, Université de Saint-Boniface, Winnipeg, Manitoba, Canada.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bernier
authors.affiliation: Laboratory for Drug Delivery and Biomaterials, College of Pharmacy, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada emmanuel_ho@umanitoba.ca.
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Ho
mesh_terms: D000282:Administration, Intravaginal; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects / Q000382:microbiology; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology*; D007778:Lactobacillus / Q000187:drug effects* / Q000254:growth & development; D011140:Polyurethanes; D019346:Sodium Acetate; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014621:Vagina / Q000166:cytology / Q000187:drug effects / Q000382:microbiology
chemical_list: D003692:Delayed-Action Preparations; D011140:Polyurethanes; D019346:Sodium Acetate; D006886:Hydroxychloroquine