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.
Kaneda
Yoshihisa
Y
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tsutsumi
Yasuo
Y
Yoshioka
Yasuo
Y
Kamada
Haruhiko
H
Yamamoto
Yoko
Y
Kodaira
Hiroshi
H
Tsunoda
Shin-ichi
S
Okamoto
Takayuki
T
Mukai
Yohei
Y
Shibata
Hiroko
H
Nakagawa
Shinsaku
S
Mayumi
Tadanori
T
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