{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T14:50:50Z","timestamp":1766760650329,"version":"3.37.3"},"reference-count":28,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["R44 HD0902206"],"award-info":[{"award-number":["R44 HD0902206"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Sex Transm Infect"],"accepted":{"date-parts":[[2023,1,7]]},"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Polyphenylene 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 against<jats:italic>Neisseria gonorrhoeae<\/jats:italic>in vitro and in a gonorrhoea mouse model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The minimal inhibitory concentration (MIC) of PPCM was determined against 11<jats:italic>N. gonorrhoeae<\/jats:italic>strains by agar dilution and a microtitre plate-based method. In vivo efficacy was tested in a murine model of<jats:italic>N. gonorrhoeae<\/jats:italic>genital tract infection by applying Yaso-GEL, PPCM incorporated in 2.7% hydroxyethylcellulose (HEC), or the HEC vehicle vaginally prior to challenge with<jats:italic>N. gonorrhoeae<\/jats:italic>. Vaginal swabs were quantitatively cultured over 5\u2009days to assess efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>PPCM MIC against<jats:italic>N. gonorrhoeae<\/jats:italic>ranged between 5\u2013100\u2009\u00b5g\/mL (agar dilution) and 50\u2013200\u2009\u00b5g\/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 of<jats:italic>N. gonorrhoeae<\/jats:italic>with PPCM increased membrane permeability, suggesting PPCM directly compromises<jats:italic>N. gonorrhoeae<\/jats:italic>viability, which may be a mechanism by which PPCM inhibits<jats:italic>N. gonorrhoeae<\/jats:italic>infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Yaso-GEL containing the API PPCM showed significant activity against<jats:italic>N. gonorrhoeae<\/jats:italic>in 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.<\/jats:p><\/jats:sec>","DOI":"10.1136\/sextrans-2022-055596","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T17:45:55Z","timestamp":1683567955000},"page":"409-415","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Polyphenylene carboxymethylene (PPCM), the active component of the topical contraceptive Yaso-GEL, exhibits potent antimicrobial activity against<i>Neisseria gonorrhoeae<\/i>in preclinical studies"],"prefix":"10.1136","volume":"99","author":[{"given":"Michelle","family":"Pilligua-Lucas","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rok","family":"Tkavc","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah K","family":"Bash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara B","family":"North","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary B","family":"Weitzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5118-3172","authenticated-orcid":false,"given":"Ann E","family":"Jerse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"2024102610500796000_99.6.409.1","unstructured":"World Health Organization . Multi-drug resistant gonorrhea fact sheets. 2021. Available: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/multi-drug-resistant-gonorrhoea"},{"key":"2024102610500796000_99.6.409.2","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1186\/s12879-021-06381-4","article-title":"Gonorrhoea: a systematic review of prevalence reporting globally","volume":"21","author":"Whelan","year":"2021","journal-title":"BMC Infect Dis"},{"key":"2024102610500796000_99.6.409.3","doi-asserted-by":"crossref","DOI":"10.1002\/jia2.25355","article-title":"Sexually transmitted infections and hiv in the era of antiretroviral treatment and prevention: the biologic basis for epidemiologic synergy","volume":"22 Suppl 6","author":"Cohen","year":"2019","journal-title":"J Int AIDS Soc"},{"key":"2024102610500796000_99.6.409.4","doi-asserted-by":"crossref","first-page":"7419","DOI":"10.1016\/j.vaccine.2018.02.081","article-title":"Biological feasibility and importance of a gonorrhea vaccine for global public health","volume":"37","author":"Vincent","year":"2019","journal-title":"Vaccine"},{"key":"2024102610500796000_99.6.409.5","doi-asserted-by":"crossref","unstructured":"Young IC , Benhabbour SR . n.d. Multipurpose prevention technologies: oral, parenteral, and vaginal dosage forms for prevention of HIV\/stis and unplanned pregnancy. 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