Calado, Rita D.A.Mendes, Bárbara B.Conniot, JoãoRavasco, João M.J.M.Sobral, DanielFerreira, CarolinaFerreira, RitaRodrigues, João CarlosSantos, DanielaDuarte, SílviaVieira, LuísInácio, Ângela S.Carrêlo, HenriqueVaz, Winchil L.C.Gomes, João PauloNunes, AlexandraConde, JoãoVieira, Otilia V.2025-02-242025-02-242024-06-05Matter. 2024 Jun 5;7(6):2205-35. doi:10.1016/j.matt.2024.04.0372590-2385http://hdl.handle.net/10400.18/10380Sexually transmitted infections and urogenital-perinatal infections are significant health challenges owing to their asymptomatic nature, multidrug-resistant pathogens, and lack of effective vaccines. Surfactants are under investigation as potential antimicrobial agents and alternatives to traditional antibiotics. Here, we discovered that N-dodecylpyridinium bromide (C12PB), a cationic quaternary ammonium surfactant, has very low potential to induce antimicrobial resistance with no antibiotic cross-resistance or inflammation in vitro. Therefore, we developed a preclinical antibiotic-free cationic surfactant-based cellulose hydrogel for treating sexually transmitted infections. The C12PB-hydrogels provided sustained surfactant release, enhancing their biocompatibility and antibacterial activity without inflammation or epithelial disruption of the vaginal tract. In a preclinical model of Neisseria gonorrhoeae infection, a single application of the C12PB-hydrogel showed a 2- to 3-fold reduction in infection. This lays the foundation for the future development of C12PB-hydrogels for sexually transmitted infections, demonstrating potent antibacterial activity and minimal risk of antimicrobial resistance or inflammation.Highlights: - The C12PB-hydrogel reduces the risk of sexually transmitted infections; - Low antimicrobial resistance potential was demonstrated; - Inflammation or epithelial disruption was not observed; - Potent against Neisseria gonorrhoeae with no vaginal microbiome alterations.Progress and potential: Our study reveals an antibiotic-free cationic surfactant-based cellulose hydrogel, the C12PB-hydrogel, demonstrating potent antibacterial activity and minimal risk of antimicrobial resistance or inflammation for treating sexually and perinatally transmitted infections. Our preclinical model showed a significant reduction in Neisseria gonorrhoeae infection with no effect on the native vaginal microbiome, representing a promising alternative treatment strategy in the face of rising antibiotic resistance and the urgent need for effective, safe antimicrobials. Our findings not only lead to safer sexual health interventions but also highlight the importance of materials science combined with biology and preclinical testing in addressing global health challenges and aligning with sustainable healthcare goals.engSexually Transmitted InfectionsPerinatal Transmitted InfectionsAntimicrobial ResistanceNeisseria gonorrhoeaeStreptococcus agalactiaeHydrogelSurfactantAntibiotic-freeInfecções Sexualmente Transmissíveisjournal article10.1016/j.matt.2024.04.002