The targeting of anionized polyvinylpyrrolidone to the renal system.
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.
Kodaira
Hiroshi
H
Graduate School of Pharmaceutical Sciences, Department of Biopharmaceutics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tsutsumi
Yasuo
Y
Yoshioka
Yasuo
Y
Kamada
Haruhiko
H
Kaneda
Yoshihisa
Y
Yamamoto
Yoko
Y
Tsunoda
Shin-ichi
S
Okamoto
Takayuki
T
Mukai
Yohei
Y
Shibata
Hiroko
H
Nakagawa
Shinsaku
S
Mayumi
Tadanori
T
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*
D000838:Anions; D004337:Drug Carriers; D011205:Povidone