Effect of deoxycholic acid-modified MPEG-oligo-chitosan micelles on the delivery, anti-biofilm activity and ROS induction of ketoconazole against C. albicans

In the study, deoxycholic acid (DXC) was linked to methoxy poly(ethylene glycol)-oligo-chitosan (MPEG-oligo-CS) to yield DXC-modified MPEG-oligo-CS (MPEG–CS–DXC) polymers as carriers to prepare ketoconazole-loaded micelles (KET-M) through thin membrane hydration, and the effect of the amount of DXC on the KET loading was studied. We also performed hemolysis, in vitro release, in vitro antifungal activity and in vivo dermatokinetic evaluation experiments. It was found that KET-M with high encapsulation efficiency and good stability was obtained when the molar ratio of DXC to MPEG-oligo-CS was 2, and there was interaction between the polymer and red blood cells. The drug release from KET-M fitted Peppas-Sahlin model and was controlled by the drug diffusion through the polymeric matrix. The KET-M showed good in vitro antifungal activity against C. albicans. KET-M could stimulate more generation of reactive oxygen species and had a better antibiofilm activity than free KET due to DXC-induced interaction with cell membrane. Dermatokinetic evaluation showed that KET-M could make KET deposited in the skin. So, the MPEG–CS–DXC polymer will be a potential carrier for improving the efficiency of skin fungal infections.