title: Dexamethasone dipropionate loaded nanoparticles of α-elastin-g-PLGA for potential treatment of restenosis.
abstract: A graft copolymer of α-elastin with poly(lactic-co-glycolic) acid (PLGA) has been synthesized and successfully employed to produce nanoparticles. Exploiting the known biological activity of α-elastin to promote the maintenance of smooth muscle cells (SMCs) contractile phenotype and the antiproliferative effect of glucocorticoids, the aim of this research was to produce drug-loaded nanoparticles suitable for potential treatment of restenosis. In particular, nanoparticles of α-elastin-g-PLGA with a mean size of 200 nm have been produced and loaded with dexamethasone dipropionate (10% w/w), chosen as a model drug that inhibits proliferation of vascular SMCs. These nanoparticles are able to prolong the drug release and show a pronounced sensibility to elastase. Drug unloaded nanoparticles stimulate the differentiation of human umbilical artery smooth muscle cells (HUASMCs) toward the contractile phenotype as demonstrated by immunofluorescence, flow cytofluorimetric, and western blotting analyses. Finally, drug-loaded nanoparticles efficiently reduce viability of HUASMCs as evidenced by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Plesso di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo , Via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Fabio S
authors.initials: FS
authors.lastname: Palumbo
authors.forename: Salvatrice
authors.initials: S
authors.lastname: Rigogliuso
authors.forename: Giulio
authors.initials: G
authors.lastname: Ghersi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Pitarresi
authors.forename: Calogero
authors.initials: C
authors.lastname: Fiorica
authors.forename: Fiorica
authors.initials: F
authors.lastname: Calogero
authors.forename: Mauro
authors.initials: M
authors.lastname: Di Stefano
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
mesh_terms: D000818:Animals; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D023903:Coronary Restenosis / Q000188:drug therapy*; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D004549:Elastin / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D004549:Elastin; C059542:dexamethasone dipropionate