The neutral condition is conducive to the yeast to mycelium transformation of C. albicans and induces biofilm formation. Acidic environment can promote the growth of yeast C. albicans and phospholipase expression, and obviously affect the antifungal activity of ketoconazole (KET). In the study, KET-loaded nanostructure hybrid lipid capsules (KET-nHLCs) comprising soybean lecithin, HS15 and ethyl -linolenate were prepared using thin film hydration method. The effect of pH on the release and antifungal activity of KET-nHLCs was investigated. The encapsulation efficiency of KET-nHLCs was 91.53±1.24%, and the water-solubility of KET in KET-nHLCs group was enhanced to 158-fold higher than that for crude KET. KET-nHLCs could control in vitro drug release at pH 4.5/7.4, 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 g/mL at pH 7.4, and were 2 and 4 g/mL pH 4.5, respectively. Interestingly, KET-nHLCs more effectively inhibited the yeast-hyphae transformation and had a better antibiofilm activity than crude KET. So, the nHLCs delivery system containing soybean lecithin should have potential application in the field of fungal infection treatment.

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