Lipid core nanoparticles as vehicle for docetaxel reduces atherosclerotic lesion, inflammation, cell death and proliferation in an atherosclerosis rabbit model

Vascular Pharmacology
B C MeneghiniRaul C Maranhão

Abstract

Chemotherapeutic agents used in cancer treatment associated to nanoparticles (LDE) that mimic the composition of low-density lipoprotein and buffer their toxicity can have strong anti-atherosclerosis action, as we showed in cholesterol-fed rabbits. Here, a novel preparation of docetaxel (DTX) carried in LDE was evaluated. Eighteen rabbits were fed 1% cholesterol during 8 weeks. After the first 4 weeks, 9 animals were treated for 4 weeks with intravenous LDE-DTX (1 mg/kg/week) and 9 with LDE only (controls) once a week for 4 weeks. Animals were then euthanized and the aortas were analyzed for morphometry, immunohistochemistry and Western blot. LDE-DTX treated group showed 80% reduction of atheroma area compared to controls. LDE-DTX treatment reduced in 60% the protein expression of macrophage marker CD68 and of MCP-1 in 80%. LDE-DTX pronouncedly lowered expression of pro-inflammatory markers NF-κB, TNF-α, IL-1β, IL-6 and von Willebrand factor and elicited 40% reduction in cell proliferation marker PCNA. The presence of smooth muscle cells in the intima was 85% smaller than in controls. Pro-apoptotic caspase 3, caspase 9, Bax, and anti-apoptotic Bcl-2 all were reduced by LDE-DTX. Protein expression of MMP-2 and MMP-9, TGF-β, and ...Continue Reading

Citations

Aug 29, 2019·Biomolecules·Armita Mahdavi GorabiAmirhossein Sahebkar
Jan 12, 2021·Advanced Drug Delivery Reviews·Jun ChenHo-Wook Jun
Nov 11, 2020·Pharmaceutics·Artur Y PrilepskiiVladimir V Vinogradov
Apr 22, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Xinlong ZangXuehong Chen
Jul 25, 2021·Journal of Clinical Medicine·Linsey J F PetersEmiel P C van der Vorst
Jul 15, 2021·ACS Applied Materials & Interfaces·Yuan ZhongGuixue Wang
Aug 17, 2021·Journal of Nanoparticle Research : an Interdisciplinary Forum for Nanoscale Science and Technology·Caijuan DongLijun Shang

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