Synthesis and Evaluation of Water-Soluble Poly(vinyl alcohol)-paclitaxel Conjugate as a Macromolecular Prodrug(Biopharmacy)

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Paclitaxel (PTX) is an antitumor agent for the treatment of various human cancers. Cremophor EL^[○!R] and ethanol are used to formulate PTX in commercial injection solutions, because of its poor solubility in water. However, these agents cause severe allergic reaction upon intravenous administration. The aim of this study is to synthesize water-soluble macromolecular prodrugs of PTX for enhancing the therapeutic efficacy. Poly(vinyl alcohol) (PVA, 80 kDa), water-soluble synthetic polymer, was used as a drug carrier which is safe and stable in the body. The 2'-hydroxyl group of PTX was reacted with succinic anhydride and then carboxylic group of the succinyl spacer was coupled to PVA via ethylene diamine spacer, resulting the water-soluble prodrug of poly(vinyl alcohol)-paclitaxel conjugate (PVA-SPTX). The solubility of PTX was greatly enhanced by the conjugation to PVA. The release of PTX from the conjugate was accelerated at the neutral to basic conditions in in vitro release experiment. [^<125>I]-labeled PVA-SPTX was retained in the blood circulation for several days and was gradually distributed into the tumorous tissue after intravenous injection to the tumor-bearing mice. PVA-SPTX inhibited the growth of sarcoma 180 cells subcutaneously inoculated in mice. It was suggested that the water-solubility of PTX was markedly enhanced by the conjugation to PVA, and PVA-SPTX effectively delivered PTX to the tumorous tissue due to the enhanced permeability and retention (EPR) effect.

収録刊行物

  • Biological & pharmaceutical bulletin   [巻号一覧]

    Biological & pharmaceutical bulletin 31(5), 963-969, 2008-05-01  [この号の目次]

    公益社団法人日本薬学会

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各種コード

  • NII論文ID(NAID)
    110006663961
  • NII書誌ID(NCID)
    AA10885497
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    09186158
  • NDL 記事登録ID
    9474175
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-V41
  • データ提供元
    CJP書誌  NDL  NII-ELS  J-STAGE 
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