Poly(vinylpyrrolidone-co-dimethyl maleic acid) as a novel renal targeting carrier.
Poly(vinylpyrrolidone-co-dimethyl maleic acid) (PVD) was found to have high renal-targeting capability and safety as a drug carrier. To optimize the renal drug delivery system using PVD, the relationship between the molecular weight of PVD and its renal accumulation were evaluated in mice by their intravenous injection. It was found that the molecular size of 6-8 kDa was associated with the highest renal accumulation. The specific bioactivity of PVD-conjugated superoxide dismutase (SOD) relative to that of unmodified SOD gradually decreased with an increase in the degree of modification to SOD with PVD6K. The conjugated SOD (L-PVD-SOD) with the molecular size of 73 kDa, which had comparable specific bioactivity with native SOD, showed longer plasma half-life than native SOD. About sixfold more L-PVD-SOD was distributed to the kidneys than native SOD 3 h after intravenous injection, whereas extensive PVD modification did not enhance the renal accumulation of SOD. This L-PVD-SOD effectively accelerated recovery from mercuric chloride-induced acute renal failure in vivo. These results suggest that L-PVD-SOD may be the optimal derivative as a potential therapeutic agent to various renal diseases.
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yoko
Y
Yamamoto
Yasuo
Y
Tsutsumi
Yasuo
Y
Yoshioka
Haruhiko
H
Kamada
Keiko
K
Sato-Kamada
Takayuki
T
Okamoto
Yohei
Y
Mukai
Hiroko
H
Shibata
Shinsaku
S
Nakagawa
Tadanori
T
Mayumi
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D004337:Drug Carriers; D016503:Drug Delivery Systems; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008627:Mercuric Chloride / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D011759:Pyrrolidines / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D014753:Vinyl Compounds / Q000737:chemistry*
D004337:Drug Carriers; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D014753:Vinyl Compounds; C475304:poly(vinylpyrrolidone-co-dimethyl maleic anhydride); D008627:Mercuric Chloride; D013482:Superoxide Dismutase