Vulvovaginal candidiasis (VVC) affects a significant proportion of women during reproductive years, with recurrent infections posing a considerable therapeutic challenge. Conventional treatments, such as clotrimazole (Clo) administration, often require frequent application due to low aqueous solubility and rapid clearance. To address these issues, a novel hydrogel-based drug delivery system (DDS) was developed, combining β-cyclodextrins (β-CD) for Clo encapsulation and halloysite nanotubes (HNT) for curcumin (Cur) delivery. A novel hydrogel-based drug delivery system (DDS) was developed to address these limitations to enhance drug solubility, retention, and localized release. β-CD enhanced Clo's solubility and prolonged antifungal effects, while HNT ensured sustained Cur release for up to 5 days, offering anti-inflammatory, antioxidant, and antimicrobial benefits. The hydrogel matrix improved drug retention and stability, with HNT reinforcing its mechanical properties for durability under moderate strain. Microbiological tests demonstrated potent antifungal activity, with inhibition zones of 39.2 ± 0.2 mm, 39.1 ± 0.2 mm, and 42.1 ± 0.2 mm against C. krusei, C. albicans 10231, and C. parapsilosis 22019, respectively. Drug release studies revealed a rapid burst release of Clo within the first 30 min, followed by prolonged Cur release. This dual-action hydrogel targets fungal infections, oxidative stress, and inflammation, providing enhanced therapeutic outcomes and improved patient adherence.
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