Investigation of ex vivo vaginal tissue deposition and antimicrobial screening- A proof-of-concept study with doxycycline-infused in situ sol-gel for localised gonorrhoea management

Abstract

Antimicrobial resistance (AMR) associated with the leading sexually transmitted infections (STIs) such as gonorrhoea, chlamydia, and trichomoniasis has resulted in significant challenges in the prevention and treatment of these infections using current approaches. To address this, the intravaginal sol-gel platform holds immense potential, as the female reproductive tract (FRT) is the primary site of invasion and colonisation of STI-causing organisms, herein, Neisseria gonorrhoeae. The lead sol-gels, F5 and F9 demonstrate relatively low doxycycline hyclate (DOXH) tissue permeability (10.18 ± 1.56 % and 4.49 ± 1.53 %, respectively), while displaying substantive tissue deposition (2372.95 ± 135.79 µg/g and 2187.73 ± 95.29 µg/g respectively) at 8 h in ex vivo bovine vaginal mucosal tissue. Furthermore, the attenuation of the deleterious effect of DOXH by the sol-gel platform on HeLa cell viability presents it as a safe drug delivery vehicle. The distinct possibility of dose reduction is demonstrated by the negligible differences in the zone of inhibition (ZoI) for sensitive isolates of N. gonorrhoeae with half-strength (0.25 % w/w) and full-strength (0.5 % w/w) DOXH sol-gels. In summary, intravaginal delivery using engineered DOXH-infused sol-gels presents a demonstrable solution to STI prevention/treatment with the potential to reduce AMR risk through localised drug delivery, dose reduction, and increased patient compliance.