title: Adequately-Sized Nanocarriers Allow Sustained Targeted Drug Delivery to Neointimal Lesions in Rat Arteries.
abstract: In atherosclerotic lesions, the endothelial barrier against the bloodstream can become compromised, resulting in the exposure of the extracellular matrix (ECM) and intimal cells beneath. In theory, this allows adequately sized nanocarriers in circulation to infiltrate into the intimal lesion intravascularly. We sought to evaluate this possibility using rat carotid arteries with induced neointima. Cy5-labeled polyethylene glycol-conjugated polyion complex (PIC) micelles and vesicles, with diameters of 40, 100, or 200 nm (PICs-40, PICs-100, and PICs-200, respectively) were intravenously administered to rats after injury to the carotid artery using a balloon catheter. High accumulation and long retention of PICs-40 in the induced neointima was confirmed by in vivo imaging, while the accumulation of PICs-100 and PICs-200 was limited, indicating that the size of nanocarriers is a crucial factor for efficient delivery. Furthermore, epirubicin-incorporated polymeric micelles with a diameter similar to that of PICs-40 showed significant curative effects in rats with induced neointima, in terms of lesion size and cell number. Specific and effective drug delivery to pre-existing neointimal lesions was demonstrated with adequate size control of the nanocarriers. We consider that this nanocarrier-based drug delivery system could be utilized for the treatment of atherosclerosis.
authors.affiliation: Division of Vascular Surgery, Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Taniguchi
authors.affiliation: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Division of Vascular Surgery, Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Department of Vascular Surgery, Saitama Medical Center, Saitama Medical University , 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Koyama
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Chida
authors.affiliation: Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Anraku
authors.affiliation: Department of Applied Chemistry, Faculty of Engineering, Kyusyu University , 744 Moto-oka, Nishi-ku, Fukuoka 819-0395, Japan.|Center for Molecular Systems, Kyusyu University , 744 Moto-oka, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kishimura
authors.affiliation: Division of Vascular Surgery, Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Shigematsu
authors.affiliation: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|Innovation Center of Nanomedicine, Kawasaki Institute of Industry Promotion , 66-20 Horikawa-cho, Saiwai-ku, Kawasaki 212-0013, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Division of Vascular Surgery, Graduate School of Medicine, The University of Tokyo , 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D058426:Neointima / Q000188:drug therapy / Q000378:metabolism; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008823:Micelles; D025521:Tumor Suppressor Proteins; D011092:Polyethylene Glycols
keywords: atherosclerosis; drug delivery; epirubicin; nanocarrier; nanoparticle; neointimal hyperplasia