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Drug Des Devel Ther. 2014 Oct 9;8:1801-15. doi: 10.2147/DDDT.S71352. eCollection 2014.

Development of polyether urethane intravaginal rings for the sustained delivery of hydroxychloroquine.

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Laboratory for Drug Delivery and Biomaterials, Faculty of Pharmacy, University of Manitoba, Winnipeg, MB, Canada.
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.


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.


HIV/AIDS; drug release; intravaginal delivery; matrix system; microbicide; polymeric drug carrier; reservoir system

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