Rosiglitazone-loaded nanospheres for modulating macrophage-specific inflammation in obesity.

Autor: Di Mascolo D; Department of Translational Imaging and Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave, Houston 77030, USA., J Lyon C, Aryal S, Ramirez MR, Wang J, Candeloro P, Guindani M, Hsueh WA, Decuzzi P
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2013 Sep 28; Vol. 170 (3), pp. 460-8. Date of Electronic Publication: 2013 Jun 18.
DOI: 10.1016/j.jconrel.2013.06.012
Abstrakt: PPARγ nuclear receptor agonists have been shown to attenuate macrophage inflammatory responses implicated in the metabolic complications of obesity and in atherosclerosis. However, PPARγ agonists currently in clinical use, including rosiglitazone (RSG), are often associated with severe side effects that limit their therapeutic use. Here, 200nm PLGA/PVA nanospheres were formulated for the systemic delivery of RSG specifically to macrophages. RSG was encapsulated with over 50% efficiency in the hydrophobic PLGA core and released specifically within the acidifying macrophage phagosomes. In bone marrow derived macrophages, RSG-loaded nanoparticles (RSG-NPs) induce a dose dependent upregulation (1.5 to 2.5-fold) of known PPARγ target genes, with maximal induction at 5μM; and downregulate the expression of genes related to the inflammatory process, with a maximum effect at 10μM. In Ldlr(-/-) mice fed high fat diet, treatment with RSG-NPs alleviated inflammation in white adipose tissue and liver but, unlike treatment with free RSG, did not alter genes associated with lipid metabolism or cardiac function, indicating a reduction in the RSG side effect profile. These biocompatible, biodegradable RSG-NPs represent a preliminary step towards the specific delivery of nuclear receptor agonists for the treatment of macrophage-mediated inflammatory conditions associated with obesity, atherosclerosis and other chronic disease states.
(Copyright © 2013 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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