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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.
Acknowledgments
We thank Dr Neal M Davies for access to his HPLC equipment. We also thank Ms Dan Zhang from the Department of Clinical Pharmacology, Aerospace Center Hospital, in the People’s Republic of China, and Ms Sidi Yang for their assistance with the RP-HPLC analysis of HCQ and drug extraction. This work was supported in part by a Canadian Institutes of Health Research Operating Grant (MOP110981) awarded to E.A.H., a grant from the Bill and Melinda Gates Foundation (OPP1007233GCE) awarded to E.A.H., and a Canadian Institutes of Health Research Canadian HIV Vaccine Initiative Grant (OCH-126275) awarded to K.R.F. Y.C. was supported by a graduate studentship from the Manitoba Health Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Disclosure
The authors report no conflicts of interest in this work.