Preclinical assessment of an antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatal transmitted infections

Sexually transmitted infections (STIs) and urogenital perinatal infections (UGIs) of bacterial origin represent an enormous burden on the health and well-being of individuals and communities. The asymptomatic character of most of these infections together with the significant increase in multidrug-resistant pathogens, and the lack of effective vaccines, makes the treatment and prevention of STIs and UGIs a big health challenge. In recent years, surfactants have been investigated for their potential use as antimicrobial agents against bacterial infections and are a promising alternative to traditional antibiotics, which are increasingly falling short due to rising bacterial resistance. Here, we discovered that N-dodecylpyridinium bromide (C12PB), a cationic quaternary ammonium surfactant has a very low/slow potential of inducing antimicrobial resistance, and do not show antibiotic cross-resistance or inflammation in vitro. For this reason, we developed a preclinical antibiotic-free cationic surfactant-based cellulose hydrogel for sexually and perinatal transmitted infections. The resultant C12PB-hydrogels provided a sustained surfactant release, enhancing their biocompatibility and antibacterial activity in the absence of inflammation or epithelial disruption of the vaginal tract. Importantly, in a preclinical model of Neisseria gonorrhoeae infection, a single application of the C12PB-hydrogel showed a 2- to 3-fold infection reduction. This lays the foundation for future development of C12PB-hydrogels for sexually transmitted infections, which exhibit potent antibacterial activity and minimal risk of antimicrobial resistance or inflammation, reducing Neisseria gonorrhoeae infection.