title: Effective attenuation of vascular restenosis following local delivery of chitosan decorated sirolimus liposomes.
abstract: Assuring the efficient local delivery via biocompatible nanosystems can be considered as a promising therapy for restenosis. The aim of the present study was preparation, in vitro characterization, and in vivo efficacy evaluation of sirolimus containing chitosan decorated liposomes for restenosis treatment. Liposomes were coated with chitosan, leading to ∼38nm increase in the particle size and a positive shift in the zeta potential from -1mV to +21mV. Chitosan modification was also confirmed by TEM, increased stability against detergent solubilization, and FTIR analyses. High entrapment efficiency (≥83%) and sustained release behaviors were demonstrated in both coated and uncoated vesicles. Compared to control groups, treatment of balloon injured rats with uncoated and chitosan-coated liposomes (50μg sirolimus) significantly reduced stenosis by 39% and 62%, respectively. The effect was also confirmed by immunohistochemical and in vivo CT angiography imaging studies. Chitosan-coated liposomes could be a novel platform for restenosis treatment.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Haeri
authors.affiliation: Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Sadeghian
authors.affiliation: Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Rabbani
authors.affiliation: Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam Sotoudeh
authors.initials: MS
authors.lastname: Anvari
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Ghassemi
authors.affiliation: Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Radfar
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Sdadashzadeh@sbmu.ac.ir.
authors.forename: Simin
authors.initials: S
authors.lastname: Dadashzadeh
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D006083:Graft Occlusion, Vascular / Q000188:drug therapy*; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D020123:Sirolimus / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D048271:Chitosan; D020123:Sirolimus
keywords: Chitosan; Liposome; Local delivery; Restenosis; Sirolimus