title: The targeting of anionized polyvinylpyrrolidone to the renal system.
abstract: We reported that the co-polymer composed of vinylpyrrolidone and maleic acid selectively distributed into the kidneys after i.v. injection. To further optimize the renal drug delivery system, we assessed the renal targeting capability of anionized polyvinylpyrrolidone (PVP) derivatives after intravenous administration in mice. The elimination of anionized PVP derivatives from the blood decreased with increasing anionic groups, and the clearance of carboxylated PVP and sulfonated PVP from the blood was almost similar. But carboxylated PVP efficiently accumulated in the kidney, whereas sulfonated PVP was rapidly excreted in the urine. The renal levels of carboxylated PVP were about five-fold higher than sulfonated PVP. Additionally, carboxylated PVP was effectively taken up by the renal proximal tubular epithelial cells in vivo after i.v. injection. These anionized PVP derivatives did not show any cytotoxicity against renal tubular cells and endothelial cells in vitro. Thus, these carboxylated and sulfonated PVPs may be useful polymeric carriers for drug delivery to the kidney and bladder, respectively.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Department of Biopharmaceutics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kodaira
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kamada
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okamoto
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mukai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shibata
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Tadanori
authors.initials: T
authors.lastname: Mayumi
mesh_terms: D000818:Animals; D000838:Anions; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008805:Mice, Inbred A; D009928:Organ Specificity; D011205:Povidone / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D012509:Sarcoma / Q000473:pathology*
chemical_list: D000838:Anions; D004337:Drug Carriers; D011205:Povidone