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Abstract

Vaginal yeast infections, such as vulvovaginal candidiasis (VVC), affect nearly three out of four women worldwide. Reoccurrence is frequent and requires repeated treatments with oral, antifungal medications at high doses. Prolonged treatments contribute to development of resistant fungal strains and the risk of systemic adverse effects. Vaginal drug delivery can overcome several of the disadvantages associated with oral drug administration. However, current dosage forms, such as vaginal creams and gels, are rapidly expelled from the vaginal tract and require daily dosing to ensure therapeutic outcome, thus jeopardizing patient compliance. Therefore, we developed rapidly dissolving microneedle arrays with a microneedle height reduction by 50% within 5 min, for local, vaginal delivery of antifungal drugs. Clotrimazole, a poorly water-soluble antifungal agent, was formulated in lipid-based nanocarriers (LNCs) and incorporated in the tips of microneedles. The antifungal activity was then tested against the most common VVC fungal strains, C. albicans and C. glabrata, using an in vitro disk diffusion assay and an explant model from bovine vaginal tissue. LNC loaded microneedles showed consistent significant inhibition of Candida spp. in comparison to blank microneedles and LNCs alone, with an inhibition diameter of 20-30 mm in vitro and a reduction of 3-5-fold fungal colonies ex vivo. Notably, the LNC-loaded microneedles inhibited fungal growth at a 10-fold lower drug dose than a commercial clotrimazole cream. Finally, a device prototype was developed in the form of an intravaginal ring incorporating multiple microneedle arrays on its surface, delivering a total drug dose of 0.1 mg per ring with 600 mu m microneedle height. Local vaginal drug delivery using such microneedle-based devices could enable more effective treatment strategies for VVC.

Keywords

lipid-based formulation; liposome; poorly water-solubledrug; dissolvable microneedles; vaginal drug delivery

Published in

Molecular Pharmaceutics
2026
Publisher: AMER CHEMICAL SOC

SLU Authors

UKÄ Subject classification

Pharmaceutical Sciences

Publication identifier

  • DOI: https://doi.org/10.1021/acs.molpharmaceut.5c01721

Permanent link to this page (URI)

https://res.slu.se/id/publ/146623