Effect of unsaturated fatty acids on the topical delivery of caspofungin ufasomes: In vitro/ Ex vivo evaluation and anti-fungal study against Candida albicans

Abstract

Cutaneous candidiasis presents a considerable challenge in today’s medical landscape, particularly for patients with weakened immune systems or chronic illnesses. As antifungal resistance continues to rise, the development of new topical therapies has become increasingly urgent. Caspofungin (CSP), an echinocandin antifungal, exhibits fungicidal activity against Candida species by inhibiting β-1,3-d-glucan synthase, a key enzyme in fungal cell wall synthesis. However, its poor stability and requirement for intravenous administration limit its clinical application. To address these limitations, novel formulations such as ufasomes (unsaturated fatty acid vesicles) have been developed to enhance caspofungin's stability and skin penetration. In this study, ufasomes were prepared using three oils: oleic acid, linoleic acid, and palmitoleic acid, along with caspofungin and cholesterol, using the thin-film method. Among the formulations, F34, composed of 500 mg palmitoleic acid and 10 mg cholesterol, exhibited promising results. It demonstrated a particle size (PS) of 87.65± 2.65 nm, a polydispersity index (PDI) of 0.22 ± 0.00, a zeta potential (ZP) of -7.46± 0.4 mV, a drug content of 97 ± 1.34 %, and an encapsulation efficiency (EE %) of 92 ± 0.82 %. Furthermore, the optimized formulation F34 showed a sustained drug release of 81.5 ± 0.4 over 600 min (10 h) compared to 100 %±0.01 of caspofungin. The permeation of F34 in 600 min (10 h) was 94 %±0.81 compared to the caspofungin 87.85 %±0.85. The antifungal activity showed that the inhibition zone diameter, MIC and MBC for caspofungin-loaded ufasomes was 29 mm±0.8, 0.153 μg/mL±0.01, 0.283 μg/mL±0.02 compared to 25 mm±0.8, 0.214 μg/mL±0.01, 0.409±0.01 for pure caspofungin. The histopathological study revealed a positive response towards the optimized formulation. In conclusion, this optimized formulation holds potential as a novel therapeutic approach for treating topical fungal infections.