Fundamental study on molecular design of bioconjugated drugs with water-soluble polymeric modifiers: Influence of electric charge on pharmacokinetics of water-soluble polymers.

DOI 1 Citations 15 References

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  • 水溶性高分子によるハイブリッド化医薬品の創製　　水溶性高分子の生体内挙動特性と荷電官能基の連関評価
  • Influence of electric charge on pharmacokinetics of water-soluble polymers
  • —水溶性高分子の生体内挙動特性と荷電官能基の連関評価—

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Abstract

In order to achieve optimum drug delivery for clinical application, the bioconjugated drugs with polymeric modifiers must be designed to show desirable biopharmaceutical characteristics. Pharmacokinetics of bioconjugated drugs is greatly affected by physicochemical characteristics of polymeric modifiers themselves. Therefore, it is very important to study the relationships between pharmacokinetics of polymeric modifiers and their physicochemical properties typified with molecular weight, electric charge, and hydrophilic-lipophilic balance and so on. In the present study, we synthesized two anionized polyvinylpyrrolidone (PVP) by radical copolymerization between vinylpyrrolidone monomer and acrylic acid or vinylsulfonic acid co-monomer to assess the influence of anionic groups on pharmacokinetics of polymeric modifiers. The resulting anionized PVPs were eliminated from the circulation more rapidly than nonionic PVP. An increase of negative charge on polymeric modifier occurred a decrease of circulation life-time. In addition, though PVP showed no specific tissue distribution, anionized PVP was markedly accumulated to kidney at 3 hr after iv injection. These fundamental approach will enable to chose the optimum polymeric modifiers for features of drugs or for purposes of bioconjugation.

Journal

  • Drug Delivery System

    Drug Delivery System 12 (6), 431-437, 1997

    THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM

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