title: Factors influencing in vivo disposition of polymeric micelles on multiple administrations.
abstract: Lactosome is a polymeric micelle composed of amphiphilic polydepsipeptide, poly(sarcosine)64-block-poly(l-lactic acid)30 (AB-type), which accumulates in solid tumors through the enhanced permeability and retention (EPR) effect. However, lactosome on multiple administrations changed its pharmacokinetics from accumulation in tumors to liver due to the production of antilactosome IgM, which was triggered by the first administration. This phenomenon is called the accelerated blood clearance (ABC). In order to reduce the production of antilactosome IgM, a novel nanoparticle composed of (poly(sarcosine)23)3-block-poly(l-lactic acid)30 (A3B-type) was prepared. The A3B-type lactosome at the second administration showed an in vivo disposition similar to that at the first administration due to suppression of antibody production. This study involving the AB- and A3B-type lactosomes, with variation of conditions, revealed that the high local density of poly(sarcosine) chains of the A3B-type lactosome should relate to the prevention of a polymeric micelle from interacting B-cell receptors.
authors.affiliation: Department of Experimental Therapeutics, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital , 53 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Hara
authors.affiliation: Clinical Division of Diagnostic Radiology, Kyoto University Hospital , 53 Shogoin-kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Division of Molecular Imaging, Biomedical Imaging Research Center, University of Fukui , 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Makino
authors.affiliation: Technology Research Laboratory, Shimadzu Corporation , 3-9-4 Hikari-dai, Seika-cho, Soraku-gun, Kyoto 619-0237, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Hara
authors.affiliation: Technology Research Laboratory, Shimadzu Corporation , 3-9-4 Hikari-dai, Seika-cho, Soraku-gun, Kyoto 619-0237, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ozeki
authors.affiliation: Department of Material Chemistry, Graduate School of Engineering, Kyoto University , Kyoto daigaku-katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Kimura
keywords: ABC phenomenon; IgM; Molecular imaging; block polymer; nanoparticle; pharmacokinetics