title: Effective accumulation of poly(vinylpyrrolidone-co-vinyl laurate) into the spleen.
abstract: To optimize polymer-conjugated drugs as a polymeric drug delivery system, it is essential to design polymeric carriers with tissue-specific targeting capacity. Previously, we showed that polyvinylpyrrolidone (PVP) was the most suitable polymeric carrier for prolonging the blood-residency of drugs, and was one of the best parent polymers to design the polymeric carriers with targeting capacity. In this study, we synthesized some hydrophobic PVP derivatives, poly(vinylpyrrolidone-co-styrene) [poly(VP-co-S)] and poly(vinylpyrrolidone-co-vinyl laurate) [poly(VP-co-VL)], and assessed their biopharmaceutical properties after intravenous administration in mice. The elimination of hydrophobic PVP derivatives from blood was the same as PVP, and the plasma half-lives of poly(VP-co-S) were almost similar to that of poly(VP-co-VL). Poly(VP-co-VL) efficiently accumulated in the spleen, whereas poly(VP-co-S) effectively accumulated in the liver. The level of poly(VP-co-VL) in the spleen was about 20 times higher than PVP and poly(VP-co-S). These hydrophobic PVP derivatives did not show any cytotoxicity against endothelial cells in vitro. Thus, poly(VP-co-VL) may be a useful polymeric carrier for drug delivery to the spleen. This study will provide useful information to design optimal polymeric carriers with targeting capacity to the spleen and liver.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mukai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shibata
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okamoto
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kamada
authors.forename: Keiichi
authors.initials: K
authors.lastname: Koizumi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Yu
authors.initials: Y
authors.lastname: Mu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kodaira
authors.forename: Keiko
authors.initials: K
authors.lastname: Sato-Kamada
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Tadanori
authors.initials: T
authors.lastname: Mayumi
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005453:Fluorescence; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008422:Materials Testing; D051379:Mice; D008968:Molecular Conformation; D011205:Povidone / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D013154:Spleen / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D011205:Povidone