title: Determination of polymeric micelles' structural characteristics, and effect of the characteristics on pharmacokinetic behaviors.
abstract: We evaluated structural factors characterizing PEG-b-P(Asp-Bzl) micelles including core size, aggregation number (Nagg), and core surface PEG density by means of small-angle X-ray scattering (SAXS), field flow fractionation with multi-angle light scattering (FFF-MALS) analysis, and DLS. Furthermore, we evaluated the stability of PEG-b-P(Asp-Bzl) micelles by means of GPC. This paper reports the correlation between the evaluated micelles' structural factors and the micelles' behaviors including the micelles' in vivo pharmacokinetic behaviors. One micelle PEG(12)-b-P(Asp-Bzl) (PEG=12,000) exhibited a high core surface density (~0.99 chain/nm(2)). In these circumstances, PEG(12)-b-P(Asp-Bzl) micelles exhibited a highly stretched PEG brush form. However, the evaluated core surface PEG densities could not fully explain the micelles' in vivo pharmacokinetic behaviors. In contrast, GPC will become a strong tool for predicting PEG(12)-b-P(Asp-Bzl) micelles' in vivo behaviors, as well as the micelles' in vitro behaviors. The stability results correlated strongly with the area-under-the-curve (AUC) values of PEG-b-P(Asp-Bzl) micelles' in vivo pharmacokinetics. Finally, we evaluated PEG(12)-b-P(Asp-Bzl) micelles' most effective structural factor for determining the micelles' behaviors, and the micelles' outermost shell surface's PEG density (DOS, PEG) correlated with the micelles' behaviors. We revealed that the evaluated DOS, PEG is the most important factor for understanding PEG(12)-b-P(Asp-Bzl) micelles' behaviors.
authors: Medical Engineering Laboratory, Research Center for Medical Sciences, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.
authors: Kouichi
authors: K
authors: Shiraishi
authors: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
authors: Yusuke
authors: Y
authors: Sanada
authors: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
authors: Shinichi
authors: S
authors: Mochizuki
authors: Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
authors: Kumi
authors: K
authors: Kawano
authors: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan.
authors: Yoshie
authors: Y
authors: Maitani
authors: Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka 808-0135, Japan. Electronic address: sakurai@kitakyu-u.ac.jp.
authors: Kazuo
authors: K
authors: Sakurai
authors: Medical Engineering Laboratory, Research Center for Medical Sciences, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: masajun2093ryo@jikei.ac.jp.
authors: Masayuki
authors: M
authors: Yokoyama
mesh_terms: D000818:Animals; D001215:Asparaginase; D001224:Aspartic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics*; D004951:Esterification; D008264:Macrophages / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics*; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D008823:Micelles; D001224:Aspartic Acid; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase
keywords: Macrophage uptake; Outermost shell surface PEG density; Polymeric micelle; Small-angle X-ray scattering; Structural characteristics