title: Effect of particle size on their accumulation in an inflammatory lesion in a dextran sulfate sodium (DSS)-induced colitis model.
abstract: Taking advantage of the enhanced permeation and retention (EPR) effect is a promising approach for delivering macromolecules or nanoparticles to tumors. Recent studies revealed that this strategy is also applicable for targeting other pathological lesions (i.e. inflammatory disease). In the present study, we report the optimal size of a nanoparticle for allowing the higher accumulation of a particle in an inflammatory lesion using a dextran sulfate sodium (DSS)-induced colitis model. As a nanoparticle platform, we utilized a SS-cleavable and pH-activated lipid-like material (ssPalm), that can be used to produce particles in a variety of sizes ranging from 50nm to 180nm while using the same lipid composition. In healthy mice, particle accumulation remained low regardless of size. In contrast, the accumulation in inflammatory colon tissue was enhanced depending on the progress of the inflammation. In this situation, the apparent uptake clearance accumulation of a mid-sized particle (113nm on average) was higher than that for smaller and larger (54nm and 183nm in average, respectively) ones. Therefore, controlling particle size is an important parameter for the extensive targeting of inflammatory lesion.
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita12 Nishi6, Kita-ku, Sapporo City, Hokkaido, 060-0812, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Watanabe
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita12 Nishi6, Kita-ku, Sapporo City, Hokkaido, 060-0812, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita12 Nishi6, Kita-ku, Sapporo City, Hokkaido, 060-0812, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: NOF Corporation, 3-3 Chidori-cho, Kawasaki-ku, Kawasaki, Kanagawa 210-0865, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Tange
authors.affiliation: NOF Corporation, 3-3 Chidori-cho, Kawasaki-ku, Kawasaki, Kanagawa 210-0865, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Nakai
authors.affiliation: Laboratory for Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita12 Nishi6, Kita-ku, Sapporo City, Hokkaido, 060-0812, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ohkawara
authors.affiliation: Laboratory for Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita12 Nishi6, Kita-ku, Sapporo City, Hokkaido, 060-0812, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita12 Nishi6, Kita-ku, Sapporo City, Hokkaido, 060-0812, Japan.
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
authors.affiliation: Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita12 Nishi6, Kita-ku, Sapporo City, Hokkaido, 060-0812, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-shi, Chiba 260-8675, Japan. Electronic address: akitahide@chiba-u.jp.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Akita
mesh_terms: D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects; D016264:Dextran Sulfate / Q000494:pharmacology*; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy*; D008055:Lipids / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D010316:Particle Size
chemical_list: D008055:Lipids; D016264:Dextran Sulfate
keywords: Accumulation; Colitis; Inflammation; Nanoparticles; ssPalm