Modifications in Vaginal Microbiota and Their Influence on Drug Release: Challenges and Opportunities

Abstract

Vaginal drug delivery represents an attractive alternative to achieve local and systemic effects due to the high contact surface exposed, the mucoadhesion of the epithelium, and the high innervation that facilitates the absorption of drugs into the bloodstream. However, despite the confinement of the vaginal cavity, it is an organ with a highly variable microenvironment. Mechanical alterations such as coitus, or chemical changes such as pH and viscosity, modify the release of drugs. In addition, changes in vaginal microbiota can influence the entire vaginal microenvironment, thus determining the disposition of drugs in the vaginal cavity and decreasing their therapeutic efficacy. Therefore, the influence of microorganisms on vaginal homeostasis can change the pre-established scenario for the application of drugs. This review aims to provide an explanation of normal vaginal microbiota, the factors that modify it, its involvement in the administration of drugs, and new proposals for the design of novel pharmaceutical dosage forms. Finally, challenges and opportunities directed toward the conception of new effective formulations are discussed.

Recovery of Saccharomyces cerevisiae CNCM I-3856 in Vaginal Samples of Healthy Women after Oral Administration

“…Additional future investigations could include a large-scale validation of the clinical efficacy of S. cerevisiae CNCM I-3856 for the prevention of recurrent vulvo-vaginal candidiasis. Considering also that the ability of a probiotic to migrate from intestinal to vaginal sphere is probably multifactorial and not only associated with the strain properties, the implementation of a new protocol would be the opportunity to study the influence of inter-individual morphology and genetic background, intrinsic factors such as age, smoking, ethnic groups and environmental factors (i.e., douching, sexual activity, hormonal changes periods…) on the vaginal microbiota composition [ 53 ] and the migration of a probiotic after oral administration.…”

New Opportunities for Endometrial Health by Modifying Uterine Microbial Composition: Present or Future?

“…The uterus represents an ideal organ for drug administration, possessing advantages such as the possibility of bypass first-pass metabolism, high permeability for low molecular weight drugs, considerable surface area for absorption, and rich blood supply [161]. However, the effectiveness of the site would depend on intrinsic factors that include pH, temperature, uterine fluid composition, viscosity, enzymatic metabolism, clearance, and others, together with the hormonal fluctuations throughout the menstrual cycle.…”

Promising Drug Delivery Approaches to Treat Microbial Infections in the Vagina: A Recent Update

“…The vagina is an imperative alternative site to deliver drugs locally and systemically, attributed to the high exposure of the contact surface, dense vascularization, and avoidance of gastrointestinal environment and hepatic first-pass effect [ 12 , 13 , 14 ]. However, some concerns have arisen regarding the eligibility of the vagina as a route for administration due to its highly variable microenvironment contributed to by the alterations in vaginal microbiota and the chemical changes such as pH, vaginal fluids, and vaginal mucus [ 12 , 14 , 15 ]. This poses a challenge for the development of vaginal products.…”

“…Lactobacillus sp. is determined to be the predominant microorganism in vaginal flora which renders the vaginal environment inhospitable to other pathogens by competing for nutrients and producing lactic acid [ 12 , 14 , 16 ]. Vaginal infections are the result of an imbalance in normal vaginal microbiota.…”