Paclitaxel associated with cholesterol-rich nanoemulsions promotes atherosclerosis regression in the rabbit

Abstract A cholesterol-rich nanoemulsion (LDE) that resembles LDL binds to the LDL receptors and after injection into the blood stream may concentrate in cells with LDL receptor overexpression, as occurs in neoplasias and other proliferative processes. Thus, LDE can be used as vehicle to target drug...

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Bibliographic Details
Published in:	Atherosclerosis Vol. 197; no. 2; pp. 959 - 966
Main Authors:	Maranhão, Raul C, Tavares, Elaine R, Padoveze, Amanda F, Valduga, Claudete J, Rodrigues, Debora G, Pereira, Maria D
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 01-04-2008 Elsevier
Subjects:	Animals Anticholesteremic Agents - administration & dosage Anticholesteremic Agents - pharmacology Aorta, Thoracic - drug effects Atherosclerosis (general aspects, experimental research) Atherosclerosis - drug therapy Biological and medical sciences Blood and lymphatic vessels Cardiology. Vascular system Cardiovascular Cardiovascular system Cholesterol - administration & dosage Disease Models, Animal Drug Delivery Systems Drug targeting Emulsions Emulsions - administration & dosage Investigative techniques, diagnostic techniques (general aspects) Low-density lipoprotein (LDL) receptors Male Medical sciences Paclitaxel Paclitaxel - administration & dosage Paclitaxel - pharmacology Rabbits Ultrasonic investigative techniques Low-density lipoprotein (LDL) receptors Drug targeting Emulsions Paclitaxel Antineoplastic agent Targeting Rabbit Lipids Cardiovascular disease Lagomorpha Cholesterol Vascular disease Lipoprotein LDL Vertebrata Mammalia Taxane derivatives Animal Atherosclerosis Antimitotic
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Summary:	Abstract A cholesterol-rich nanoemulsion (LDE) that resembles LDL binds to the LDL receptors and after injection into the blood stream may concentrate in cells with LDL receptor overexpression, as occurs in neoplasias and other proliferative processes. Thus, LDE can be used as vehicle to target drugs against those cells. The current study was designed to verify in rabbits whether LDE concentrates in the lesioned rabbit artery and whether a paclitaxel derivative, paclitaxel oleate, associated to LDE could reduce the atherosclerotic lesions. Sixteen male New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30 under cholesterol feeding, eight animals were treated with four weekly intravenous injections of LDE-paclitaxel (4 mg/kg) and eight with four weekly intravenous saline solution injections for additional 30 days. On day 60, the animals were sacrificed for analysis. The uptake of LDE labeled with [14 C]-cholesteryl oleate by the aortic arch of cholesterol-fed rabbits was twice as much that observed in animals fed only regular chow. LDE-paclitaxel reduced the lesion areas of cholesterol-fed animals by 60% and intima-media ratio fourfold and inhibited the macrophage migration and the smooth muscle cell proliferation and invasion of the intima. LDE-paclitaxel treatment had no toxicity. In conclusion, LDE-paclitaxel produced pronounced atherosclerosis regression without toxicity and has shown remarkable potential in cardiovascular therapeutics.
ISSN:	0021-9150 1879-1484
DOI:	10.1016/j.atherosclerosis.2007.12.051