The use of PVP as a polymeric carrier to improve the plasma half-life of drugs.
To achieve an optimum drug delivery such as targeting or controlled release utilizing bioconjugation with polymeric modifier, the conjugate between drugs and polymeric modifiers must be designed to show desirable pharmacokinetic characteristics in vivo. In this study, we assessed the biopharmaceutical properties of various nonionic water-soluble polymers as polymeric drug carriers. Polyvinylpyrrolidone (PVP) showed the longest mean resident time (MRT) after i.v. injection of all nonionic polymers with the same molecular size. In fact, tumor necrosis factor-alpha (TNF-alpha) bioconjugated with PVP (PVP-TNF-alpha) circulated longer than TNF-alpha bioconjugated with polyethylene glycol (PEG-TNF-alpha) with the same molecular size. Each nonionic polymeric modifier showed a different tissue distribution. Dextran was accumulated in the spleen and liver. Polydimethylacrylamide (PDAAm) tended to distribute in the kidney. However, PVP showed the minimum volume of tissue distribution. These results suggested that PVP is the most suitable polymeric modifier for prolonging the circulation lifetime of a drug and localizing the conjugated drug in blood.
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Yoshihisa
Y
Kaneda
Yasuo
Y
Tsutsumi
Yasuo
Y
Yoshioka
Haruhiko
H
Kamada
Yoko
Y
Yamamoto
Hiroshi
H
Kodaira
Shin-ichi
S
Tsunoda
Takayuki
T
Okamoto
Yohei
Y
Mukai
Hiroko
H
Shibata
Shinsaku
S
Nakagawa
Tadanori
T
Mayumi
D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004341:Drug Evaluation / Q000379:methods; D004355:Drug Stability; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism*; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011205:Povidone / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism
D004337:Drug Carriers; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; D011205:Povidone