Synthesis of a poly(vinylpyrrolidone-co-dimethyl maleic anhydride) co-polymer and its application for renal drug targeting.
We have synthesized a polymeric drug carrier, polyvinylpyrrolidone-co-dimethyl maleic anhydride [poly(VP-co-DMMAn)], for use in renal drug delivery. About 80% of the 10-kDa poly(VP-co-DMMAn) selectively accumulated in the kidneys 24 h after intravenous administration to mice. Although this accumulated poly(VP-co-DMMAn) was gradually excreted in the urine, about 40% remained in the kidneys 96 h after treatment. Poly(VP-co-DMMAn) was taken up by the renal proximal tubular epithelial cells and no cytotoxicity was noted. Higher doses did not produce toxicity in the kidneys or other tissues. In contrast, polyvinylpyrrolidone of the same molecular weight did not show any tissue-specific distribution. Poly(VP-co-DMMAn)-modified superoxide dismutase accumulated in the kidneys after intravenous administration and accelerated recovery from acute renal failure in a mouse model. In contrast, polyvinylpyrrolidone-modified superoxide dismutase and native superoxide dismutase were not as effective. Thus, poly(VP-co-DMMAn) is a useful candidate as a targeting carrier for renal drug delivery systems.
Kamada
Haruhiko
H
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tsutsumi
Yasuo
Y
Sato-Kamada
Keiko
K
Yamamoto
Yoko
Y
Yoshioka
Yasuo
Y
Okamoto
Takayuki
T
Nakagawa
Shinsaku
S
Nagata
Satoshi
S
Mayumi
Tadanori
T
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride; D051379:Mice; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D013482:Superoxide Dismutase / Q000008:administration & dosage; D014753:Vinyl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity
D011108:Polymers; D011759:Pyrrolidines; D014753:Vinyl Compounds; C475304:poly(vinylpyrrolidone-co-dimethyl maleic anhydride); D008627:Mercuric Chloride; D013482:Superoxide Dismutase