Understanding vaginal biofilms: The first step in harnessing antimicrobial nanomedicine

In spite of multipurpose technologies offering broad-spectrum prevention for sexually transmitted infections (STIs) and contraception, the STIs incidences rise worldwide. The situation is even more alarming considering continuous rise in antimicrobial resistance (AMR) that limits therapy options. In this review we address the specific challenges of efficiently treating vaginal infections locally, at the infection site, by understanding the underlying barriers to efficient treatment such as vaginal biofilms. Knowledge on vaginal biofilms remains, up to now, rather scarce and requires more attention. We therefore propose a 'back to basics' insight that seeks to probe the complexity and role of the vaginal microbiota, its relationship with vaginal biofilms and implications to future therapeutic modalities utilizing advanced nano delivery systems. Our key objective is to highlight the interplay between biofilm, (nano)formulation and therapy outcome rather than provide an overview of all nanoformulations that were challenged against biofilms. We focused on the anatomy of the female reproductive organ and its physiological changes from birth, the unique vaginal microenvironment in premenopausal and postmenopausal women, vaginal biofilm infections and current nanomedicine-based approaches to treat infections in the vaginal site. Finally, we offer our perspectives on the current challenges associated with vaginal delivery and key considerations that can aid in the design and development of safer and potent products against persisting vaginal infections.