A multipurpose silicone elastomer vaginal ring releasing dapivirine and Cu2+/Zn2+ ions for HIV prevention and non-hormonal contraception

A dapivirine (DPV)-releasing vaginal ring (DapiRing®, containing 25 mg DPV) has been approved in various African countries for prevention of human immunodeficiency virus type 1 (HIV-1). Current research is focused on next-generation multipurpose prevention technology (MPT) vaginal rings that additionally provide contraception, and a combination dapivirine + levonorgestrel ring is in clinical development. However, hormonal contraceptives have numerous side effects and contraindications, and many women are interested in hormone-free contraceptive options. Copper and zinc have well documented spermicidal activity; for example, copper intrauterine devices-comprising a copper metal wire fitted to a polyethylene frame and releasing cupric (Cu²⁺) ions-have a long history of use as a long-actingreversible non-hormonal form of contraception. Here, we report a multipurpose vaginal ring offering sustained release of DPV, Cu²⁺ ions, and Zn²⁺ ions. Matrix-type silicone elastomer vaginal rings containing different combinations of DPV (25 mg) and various copper/zinc substances (copper nanopowders, zinc nanopowders, copper sulphate pentahydrate, and zinc acetate dihydrate) were successfully manufactured by injection molding. DPV and the metal nanopowders were stable during manufacturing; partial dehydration occurred with copper sulphate pentahydrate and zinc acetate dihydrate. Incorporation of copper/zinc substances had minimal impact on DPV release, and the formulations produced similar DPV release compared with DapiRing®. Rings containing metal salts released significantly more Cu²⁺/Zn²⁺ ions than those containing metal nanopowders, and greater quantities of Cu²⁺/Zn²⁺ ions compared with marketed copper IUDs or experimental copper-zinc IUDs. The results demonstrate that copper/zinc metals and salts can be effectively incorporated into and released from silicone elastomer vaginal rings and are compatible with DPV. The inclusion of copper/zinc offers potential as non-hormonal contraception and warrants further investigation in the context of MPTs.