Pharmacodynamics of multifunctional evodiamine butyryl derivative-loaded lipid nanoparticles

Abstract:

Objective：To study the pharmacodynamics of multifunctional evodiamine butyryl derivative（EAB） and evodiamine butyryl derivative-loaded lipid nanoparticles（EABLNs） in rats. Methods：EABLNs were prepared by the film ultrasound method；the appear－ance，particle size，potential，and encapsulation efficiency of EABLNs were measured. Thirty-two male Sprague-Dawley rats were ran－domly divided into normal group，model group，EAB treatment group，and EABLNs treatment group；the body weight changes of the rats were monitored daily. After continuous administration by oral gavage for 1 week，followed by administration of hypoxanthine by oral gavage and subcutaneous injection of potassium oxonate，the rat model of hyperuricemia was successfully established. The rats were tested for serum levels of uric acid（UA），creatinine（CR），urea nitrogen（BUN），total cholesterol（TC），triglyceride（TG），low-den－sity lipoprotein（LDL），high-density lipoprotein（HDL），alanine aminotransferase（ALT），and aspartate aminotransferase（AST）. Mean－while，histopathological examinations were performed on the heart，liver，spleen，lung，kidney，and brain of the rats. Results：Electron microscopy showed that EABLNs were successfully prepared. Body weight curves showed that there were no differences（except for the results measured at 7 time points） in body weight between the four different groups. Biochemical analysis showed that，the levels of UA，CR，and BUN were significantly higher in the model group than in the other three groups（F=20.080，F=8.459，F=7.169；P=0.000，P=0.007，P=0.012）；there were no significant differences between the four groups in serum levels of ALT or AST（F=1.701，F=3.528；P=0.244，P=0.068），or serum levels of TC，TG，LDL，or HDL（F=3.069，F=0.398，F=0.191，F=3.291；P=0.091，P=0.758，P=0.899，P=0.079）. Histopathological examinations showed that the integrity of the renal units in the model group was seriously damaged，but the damage of the kidney induced by hyperuricemia was reversed by EABLNs，and EABLNs did not cause damage to the heart，liver，spleen，lung，or brain. Conclusion：It is the first time that EABLNs have been found to be feasible for the treatment of hyperuricemia and its complications.