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

Abstract

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.

Keywords

atherosclerosis treatment / lipid solid nanoparticles / emulsions / paclitaxel / MRI / drug targeting

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Acknowledgments

Research funding was provided by a grant from Boston University, United States, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), São Paulo, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brasília, Brazil. Lima had a scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – CAPES and express her appreciation.

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