The inhibitory effect of ketoconazole-loaded nanostructure hybrid lipid capsules on the growth and biofilm activity of C. albicans

Abstract

Neutral conditions are conducive for the yeast to mycelium transformation of C. albicans and inducing biofilm formation. Alternatively, an acidic environment can promote the growth of C. albicans yeast and phospholipase expression, and obviously affect the antifungal activity of ketoconazole (KET). In this study, KET-loaded nanostructure hybrid lipid capsules (KET-nHLCs) comprised of soybean lecithin, HS15 and ethyl α-linolenate were prepared using the thin film hydration method. Additionally, the effect of pH on the release and antifungal activity of KET-nHLCs was investigated. The encapsulation efficiency of KET-nHLCs was determined to be 91.53% ± 1.24%, and the water solubility of KET in the KET-nHLC group was enhanced by 158-fold compared to the crude KET. KET-nHLCs could control the in vitro drug release at pH 4.5/7.4, while its slow-release effect on KET was more obvious at pH 4.5. The MIC₅₀ values of KET-nHLCs and KET were 0.5 and 0.25 μg mL⁻¹ at pH 7.4 and 2 and 4 μg mL⁻¹ pH 4.5, respectively. Interestingly, KET-nHLCs more effectively inhibited the yeast-hyphae transformation and had better antibiofilm activity than crude KET. Thus, the -nHLC delivery system containing soybean lecithin has potential application in the field of fungal infection treatment.