Chrysin-loaded PCL nanocapsule spray as a topical strategy against cutaneous candidiasis

Candida albicans, the most prevalent fungal pathogen in humans, poses increasing therapeutic challenges due to rising resistance to conventional azole antifungals, driving interest in natural alternatives. Chrysin (5,7- dihydroxyflavone) is a flavonoid with promising biological activities that are limited by poor aqueous solubility and low bioavailability. This study aimed to develop and characterize chrysin-loaded poly (ε-caprolactone) (PCL) nanocapsules in a spray formulation for topical treatment of cutaneous candidiasis.

Nanocapsules were produced by interfacial deposition of the preformed polymer and characterized for particle size, zeta potential, encapsulation efficiency, and morphology. Their performance was further evaluated through in vitro release studies, antifungal activity against C. albicans, antioxidant activity, and spray performance.

The formulation exhibited nanometric size (207.6 ± 4.63 nm), low polydispersity (0.174 ± 0.04), high encapsulation efficiency (87.28% ± 0.77%), and sustained drug release over 120 h, with antifungal activity substantially superior to free chrysin, requiring 5- to 8-fold lower concentrations to achieve equivalent inhibitory and fungicidal effects, and enhanced antioxidant efficacy at lower concentrations. The spray device delivered consistent and reproducible doses (118.5% of theoretical content, RSD 5.78%). These findings demonstrate that chrysin-loaded PCL nanocapsules successfully overcome solubility limitations, enhance antifungal and antioxidant activities, and provide sustained release, representing a promising nanotechnology-based alternative for cutaneous candidiasis treatment with convenient topical application.