Abstract
ABSTRACTIn vitro interaction of osthol (Ost) and fluconazole (FLC) was investigated against 11 fluconazole-resistant clinical isolates of Candida albicans. Synergistic activities were determined using the checkerboard microdilution assay. The results of agar diffusion test confirmed the synergistic interaction. We used an enteric material Eudragit S100 for preparation of Ost nanoparticle (Ost-NP) to improve the oral bioavailability, biological activity of Ost. The physicochemical characteristics of Ost-S100-NP revealed Ost-S100-NP with mean particle size of 55.4±0.4 nm, encapsulation efficiency of 98.95±0.06%, drug loading efficiency of 23.89±0.25%, yield of 98.5±0.1% and a polydispersity index (PDI) of 0.165. As the Ost concentration-time curve showed, Ost-S100-NP can increase the plasma concentration and relative bioavailability of Ost compared with Ost-suspension by oral administration. In vivo, Ost-S100-NP enhanced the therapeutic efficacy of Ost against FLC-resistant C. albicans in immunosuppressed candidiasis mice model. The available information strongly suggests that Ost-S100-NP may be used as a promising compound against drug-resistant fungi.
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