title: Use of remote film loading methodology to entrap sirolimus into liposomes: preparation, characterization and in vivo efficacy for treatment of restenosis.
abstract: The main objective of this study was to formulate an effective controlled-release liposomal drug delivery system for sirolimus (SIR), a potent antiproliferative and anti-inflammatory drug, to be used for the treatment of restenosis following local vascular delivery. Liposomes were prepared using remote film loading method and characterized with regard to entrapment efficiency (EE), size distribution and zeta potential. The effects of key formulation and proceeding variables on both EE and drug release were studied using a fractional factorial design. By means of this entrapment technique, 98% SIR incorporation was achieved. Nanoliposomes were found to have average size of 110 nm and zeta potential of -9 mV. Developed formulations were found to have prolonged drug release for up to 3 weeks in vitro; this was best fitted by the Higuchi model. Other scopes of this work were to determine the applicability of sirolimus-loaded nanoliposomes (SIR-L) as drug carriers for the treatment of restenosis and to evaluate the effect of the presence of rigid lipids on the in vivo efficacy of the liposomal carrier of SIR. In vivo studies in balloon injured rat carotid arteries revealed the potential of SIR-loaded liposomes as efficient local and controlled drug delivery systems to reduce restenosis.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Haeri
authors.forename: Saeed
authors.initials: S
authors.lastname: Sadeghian
authors.forename: Shahram
authors.initials: S
authors.lastname: Rabbani
authors.forename: Maryam Sotoudeh
authors.initials: MS
authors.lastname: Anvari
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Boroumand
authors.forename: Simin
authors.initials: S
authors.lastname: Dadashzadeh
mesh_terms: D000818:Animals; D017536:Carotid Artery, Common; D023903:Coronary Restenosis / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D049329:Nanostructures / Q000737:chemistry; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013535:Suspensions
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D008081:Liposomes; D013535:Suspensions; D020123:Sirolimus