Beyond barriers: advances in vaginal drug delivery systems for women’s health

The vaginal route has emerged as a promising alternative to conventional drug delivery approaches, offering advantages such as ease of administration, circumvention of hepatic first-pass metabolism, and the potential to achieve both localized and systemic therapeutic effects. Nevertheless, its broader clinical adoption is limited by physiological and biological barriers, including rapid mucus clearance, acidic pH, enzymatic degradation, and the complex dynamics of the vaginal microbiota, all of which compromise drug retention and absorption. This review analyzes more than 120 studies, including conventional dosage forms, nanocarrier-based systems, and advanced controlled-release platforms. Traditional dosage forms (creams, gels, suppositories, tablets, and films) remain widely used but are often limited by leakage, frequent dosing requirements, and poor patient adherence. To overcome these challenges, nanotechnology-based delivery systems such as lipid-based carriers, polymeric nanoparticles, and stimuli-responsive nanoplatforms have been developed, improving solubility, enhancing mucosal penetration, and enabling sustained or controlled drug release. Evidences from preclinical and clinical investigations show that these systems are effective in managing vaginal infections (e.g., bacterial vaginosis, vulvovaginal candidiasis), contraception, hormone replacement therapy, and localized cancer treatment. Furthermore, advanced platforms, including vaginal rings and bioadhesive formulations, provide prolonged drug release and improved patient compliance. By integrating findings across a large body of literature, this review highlights the transformative potential of nanocarrier-based and controlled-release systems in optimizing therapeutic efficacy and advancing women’s health care.