Evaluation of atherosclerotic lesions in cholesterol-fed mice during treatment with paclitaxel in lipid nanoparticles： a magnetic resonance imaging study

摘要

Cholesterol-core nanoparticles(LDE) have been shown to be recognized by low-density lipoprotein receptors(LDLR) after administration;therefore,LDE is an ideal vehicle to deliver drug with targeting property.Paclitaxel,when incorporated into LDE,promotes atherosclerosis regression with reduced drug toxicity in rabbits through LDLR.Here,we tested whether LDE-paclitaxel could still be effective in reducing diet-induced atherosclerosis in a mouse model without LDLR.Nineteen LDLR knockout male mice were fed 1%cholesterol for 12 weeks.Then,12 animals received 4-weekly intraperitoneal LDE-paclitaxel(4 mg/kg) while 7 controls received saline solution.On week 12 and 16,in vivo MRI of the aortic roots was performed.Aorta macroscopy was made after euthanasia.Reduction of atherosclerotic lesions was observed.LDE-paclitaxel treatment resulted in reduction of wall area(14%)and stenosis(22%) by MRI and 33%by macroscopy.Thus,LDE-paclitaxel may produce pharmacological effects through LDE uptake by mechanisms other than LDLR.