Polyphenylene carboxymethylene (PPCM), the active component of the topical contraceptive Yaso-GEL, exhibits potent antimicrobial activity againstNeisseria gonorrhoeaein preclinical studies

Abstract

IntroductionPolyphenylene carboxymethylene (PPCM) is a condensation polymer that has both contraceptive and antimicrobial activity against several sexually transmitted viruses including HIV, herpes simplex virus, Ebola virus and SARS-CoV-2 in preclinical studies. PPCM, both as an active pharmaceutical ingredient (API) and in a vaginal gel formulation (Yaso-GEL), has an excellent safety profile. Here, we evaluated the efficacy of PPCM againstNeisseria gonorrhoeaein vitro and in a gonorrhoea mouse model.MethodsThe minimal inhibitory concentration (MIC) of PPCM was determined against 11N. gonorrhoeaestrains by agar dilution and a microtitre plate-based method. In vivo efficacy was tested in a murine model ofN. gonorrhoeaegenital tract infection by applying Yaso-GEL, PPCM incorporated in 2.7% hydroxyethylcellulose (HEC), or the HEC vehicle vaginally prior to challenge withN. gonorrhoeae. Vaginal swabs were quantitatively cultured over 5 days to assess efficacy.ResultsPPCM MIC againstN. gonorrhoeaeranged between 5–100 µg/mL (agar dilution) and 50–200 µg/mL (microtitre plate method). PPCM/HEC gel applied vaginally prior to bacterial challenge resulted in a concentration-dependent inhibition of infection. Yaso-GEL containing 4% PPCM prevented infection in 100% of mice. Incubation ofN. gonorrhoeaewith PPCM increased membrane permeability, suggesting PPCM directly compromisesN. gonorrhoeaeviability, which may be a mechanism by which PPCM inhibitsN. gonorrhoeaeinfection.ConclusionsYaso-GEL containing the API PPCM showed significant activity againstN. gonorrhoeaein vitro and in vivo in a female mouse model. These data support further development of Yaso-GEL as an inexpensive, non-hormonal and non-systemic product with both contraceptive and antimicrobial activity against gonorrhea and other common sexually transmitted infections (STIs). Such multipurpose prevention technology products are needed by women in all economic, social and cultural circumstances to prevent unintended pregnancy and STIs.