Liposomal Nanotherapy for Treatment of Atherosclerosis

• Published in: Advanced healthcare materials 2020-07, Vol.9 (14), p.e2000465-n/a
• Main Authors: Darwitan, Anastasia, Wong, Yee Shan, Nguyen, Luong T. H., Czarny, Bertrand, Vincent, Anita, Nedumaran, Anu Maashaa, Tan, Yang Fei, Muktabar, Aristo, Tang, Jin Kai, Ng, Kee Woei, Venkatraman, Subbu
• Format: Article
• Language: English
• Subjects: Animals; anti‐inflammation; Apolipoprotein E; Apolipoproteins E; Arteriosclerosis; Atherosclerosis; Atherosclerosis - drug therapy; Cerebral infarction; Cholesterol; Chronic illnesses; Controlled release; corticosteroid; Corticosteroids; Drug delivery; Drug delivery systems; Efflux; fluocinolone acetonide; Immune system; In vivo methods and tests; Inflammation; Lipids; Liposomes; Macrophages; Mice; Mice, Knockout; Myocardial infarction; Plaque, Atherosclerotic - drug therapy; Plaques; Sustained release
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202000465

Atherosclerosis is a chronic disease that can lead to life‐threatening events such as myocardial infarction and stroke, is characterized by the build‐up of lipids and immune cells within the arterial wall. It is understood that inflammation is a hallmark of atherosclerosis and can be a target for therapy. In support of this concept, an injectable nanoliposomal formulation encapsulating fluocinolone acetonide (FA), a corticosteroid, is developed that allows for drug delivery to atherosclerotic plaques while reducing the systemic exposure to off‐target tissues. In this study, FA is successfully incorporated into liposomal nanocarriers of around 100 nm in size with loading efficiency of 90% and the formulation exhibits sustained release up to 25 d. The anti‐inflammatory effect and cholesterol efflux capability of FA‐liposomes are demonstrated in vitro. In vivo studies carried out with an apolipoprotein E‐knockout (Apoe−/−) mouse model of atherosclerosis show accumulation of liposomes in atherosclerotic plaques, colocalization with plaque macrophages and anti‐atherogenic effect over 3 weeks of treatment. This FA‐liposomal‐based nanocarrier represents a novel potent nanotherapeutic option for atherosclerosis. A novel injectable anti‐inflammatory nanotherapy is constructed for delivery of corticosteroid to atherosclerotic plaque. Fluocinolone acetonide is encapsulated in nanoliposomes with high drug loading and sustained release capability. The nanotherapy shows anti‐inflammatory and cholesterol efflux effects on foam cells in vitro. It also shows accumulation in the atherosclerotic plaque and therapeutic efficacy in Apoe−/− mice.