Multipurpose vaginal rings for HIV prevention and treatment of bacterial vaginosis

Research output: Contribution to conferenceAbstractpeer-review


Acquired immune deficiency syndrome (AIDS) is one of the most serious global public health diseases. Vaginal microbicides are vaginally-administered pharmaceutical formulations intended to reduce or prevent sexual transmission of the human immunodeficiency virus, (HIV) virus, the causative agent of AIDS. For the past ten years, antiretroviral-releasing vaginal rings have been prioritized as a female-controlled HIV prevention method. A vaginal ring containing dapivirine (DPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is being developed as a long-acting HIV microbicide product by the International Partnership for Microbicides (IPM). Multipurpose prevention technology strategies (MPTs) aim to prevent HIV-1 infection, unintended pregnancy and other sexually transmitted infections using a single product. Bacterial vaginosis is a common lower genital tract disorder in reproductive age women and is characterized by the replacement of a Lactobacillus-dominated microbiota by a variable mixture of anaerobic and facultative bacteria. It has been reported that bacterial vaginosis is associated with an increased risk of HIV acquisition. Metronidazole (MET) inhibits nucleic acid synthesis and is the major treatment of treatment for BV. In this PhD project, we propose to develop a combination drug ring that provides sustained release of both DPV and MET to prevent HIV infection and treat or prevent bacterial vaginosis.

Matrix-type silicone elastomer vaginal rings comprising different MET loadings (100, 250, 500, 1000 and 2000 mg) and either 25 or 200 mg DPV were manufactured using a Babyplast injection molding machine. Samples of matrix silicone elastomer rings loaded either DPV, MET or combination of DPV and MET were analyzed by DSC to characterize the nature of the drugs in the rings. Four rings were randomly selected from each ring formulation for 28-day in vitro release studies in the 0.2%w/w Tween80 release media at 37˚C and 60 rpm. Mechanical tests containing shore M hardness tests, static and dynamic compression response were conducted on these different VR formulations.

After 28-day in vitro release testing, cumulative DPV release was 3.7 and 11.7 mg for rings loaded with 25 and 200 mg DPV, respectively. Cumulative MET release was 30.7, 54.0, 109, 173 and 251 mg for rings loaded with 100, 250, 500, 1000 and 2000 mg MET. In addition, DPV cumulative release was increased to 5 mg for rings loaded with both 25 mg and 1000 mg MET. The thermal results of mixtures of DPV and MET in physical mixtures and incorporating in silicone elastomers showed reduced melting transitions for both drug components, indicating a eutectic composition at 80% MET and at a temperature of 153 ˚C. Mean Shore M hardness values for DPV formulations and MET (100 and 250 mg) formulations were 36 and 34, respectively. The 500, 1000 and 2000 mg MET formulations produced values ranging from 37 to 45. All VR formulations recovered to 90–100% of their original diameter after 1000-cycle compression.

The data support the continued development of these vaginal ring formulations as multi-purpose prevention technologies (MPTs) for HIV prevention and bacterial vaginosis treatment and prevention.
Original languageEnglish
Publication statusAccepted - 2019
Event2019 Symposium of the United Kingdom & Ireland Controlled Release Society - Liverpool John Moores University, Liverpool, United Kingdom
Duration: 03 Jun 201904 Jun 2019


Conference2019 Symposium of the United Kingdom & Ireland Controlled Release Society
Abbreviated titleUKICRS2019
Country/TerritoryUnited Kingdom


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