Clotrimazole‐loaded <scp>PLGA</scp> microparticles for local drug delivery to the vagina: Shape does matter

BACKGROUND: Intravaginal drug administration is the most promising strategy for treating vaginal infections to protect women's health, such as vulvovaginal candidiasis (VVC). However, conventional vaginal formulations in the clinic face challenges such as drug leakage and low bioavailability due to the mucus barrier and vaginal self-cleaning behavior. To address these limitations, we designed and optimized clotrimazole-loaded PLGA non-spherical microparticles (CPNMs) for vaginal drug delivery. METHODS: CPNMs and clotrimazole-loaded PLGA porous microspheres (CPMs) were prepared by the double emulsion-solvent evaporation method. The physicochemical features and in vitro drug release kinetics were characterized, and the effect of shape on drug delivery were also investigated. After intravaginal administration of CPMs and CPNMs, the pharmacokinetics and biocompatibility in the vagina of mice were studied. RESULTS: Both CPMs and CPNMs exhibited sustained release features in vitro. Initially, there was a rapid release within the first 24 h and the cumulative release of CPMs and CPNMs was 46.55% and 56.89% over 7 days, respectively. Compared to CPMs, CPNMs demonstrated an extended drug release in vivo, maintaining a residence duration of at least 72 h, which was beneficial for clotrimazole delivery at a high concentration in the vagina of mice. Histological evaluation demonstrated the low cytotoxicity and good biocompatibility of CPNMs, with no obvious damage to vaginal epithelial cells. CONCLUSION: This vaginal drug delivery system offers potential applications for managing VVC, along with other health concerns in women.