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

この論文にアクセスする

この論文をさがす

著者

抄録

Paclitaxel (PTX) is an antitumor agent for the treatment of various human cancers. Cremophor EL® 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. [125I]-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

    Biological & pharmaceutical bulletin 31(5), 963-969, 2008-05-01

    公益社団法人日本薬学会

参考文献:  39件中 1-39件 を表示

  • <no title>

    WANI M. C.

    J. Am. Chem. Soc. 93, 2325-2327, 1971

    被引用文献1件

  • <no title>

    ARBUCK S. G.

    J. Natl. Cancer Inst. Monogr. 15, 11-24, 1993

    被引用文献1件

  • <no title>

    FOA R.

    Int. J. Clin. Lab. Res. 24, 6-14, 1994

    被引用文献1件

  • <no title>

    LONG H. J.

    Mayo Clin. Proc. 69, 341-345, 1994

    被引用文献1件

  • <no title>

    WIERNIK P. H.

    J. Natl. Cancer Inst. Monogr. 15, 185-187, 1993

    被引用文献1件

  • <no title>

    LEE J.

    Pharm. Res. 20, 1022-1030, 2003

    被引用文献1件

  • <no title>

    FJALLSKOG M. L.

    Lancet 342, 8873-8875, 1993

    被引用文献1件

  • <no title>

    EINZIG A. I.

    J. Clin. Oncol. 10, 1748-1753, 1992

    被引用文献1件

  • <no title>

    ROGERS B. B.

    Oncol. Nurs. Forum 20, 1483-1489, 1993

    被引用文献1件

  • <no title>

    GOLDSPIEL B. R.

    Ann. Pharmacother. 28, S23-S26, 1994

    被引用文献1件

  • <no title>

    LI C.

    Anticancer Drugs 7, 642-648, 1996

    被引用文献1件

  • <no title>

    LI C.

    Clin. Cancer Res. 5, 891-897, 1999

    被引用文献1件

  • <no title>

    SINGER J. W.

    Adv. Exp. Med. Biol. 519, 81-99, 2003

    被引用文献1件

  • <no title>

    SUGAHARA S.

    Biol. Pharm. Bull. 25, 632-641, 2002

    被引用文献1件

  • <no title>

    SEYMOUR L. W.

    Crit. Rev. Ther. Drug Carrier Syst. 9, 135-187, 1992

    被引用文献1件

  • <no title>

    MAEDA H.

    Adv. Enzyme Regul. 41, 189-207, 2001

    被引用文献1件

  • <no title>

    MAEDA H.

    Crit. Rev. Ther. Drug Carrier Syst. 6, 193-210, 1989

    被引用文献1件

  • <no title>

    MALLAPRAGADA S. K.

    Handbook of Pharmaceutical Controlled Release Technology, 2000

    被引用文献1件

  • <no title>

    HEARN M. T.

    Methods Enzymol. 135, 102-117, 1987

    被引用文献1件

  • <no title>

    HABEEB A. F.

    Anal. Biochem. 14, 328-336, 1966

    被引用文献1件

  • <no title>

    FIELDS R.

    Biochem. J. 124, 581-590, 1971

    被引用文献1件

  • <no title>

    FIELDS R.

    Methods Enzymol. 25, 464-468, 1972

    被引用文献1件

  • <no title>

    DE FRIES R.

    J. Clin. Lab. Anal. 9, 89-95, 1995

    被引用文献1件

  • <no title>

    BAEK N.

    J. Biomater. Sci. Polym. Ed. 15, 527-542, 2004

    被引用文献1件

  • <no title>

    KONNO T.

    J. Biomed. Mater. Res. A 65, 209-214, 2003

    被引用文献1件

  • <no title>

    WADA M.

    Anticancer Res. 27, 1431-1435, 2007

    被引用文献1件

  • <no title>

    CAHAN M. A.

    Cancer Chemother. Pharmacol. 33, 441-444, 1994

    被引用文献3件

  • <no title>

    PANCHAGNULA R.

    Int. J. Pharm. 172, 1-15, 1998

    被引用文献1件

  • <no title>

    GREENWALD R. B.

    J. Med. Chem. 39, 424-431, 1996

    被引用文献3件

  • <no title>

    LI C.

    Cancer Res. 58, 2404-2409, 1998

    被引用文献4件

  • <no title>

    RINGSDORF H.

    J. Polym. Sci. Polym. Symp. 51, 135-153, 1975

    被引用文献12件

  • <no title>

    YUAN F.

    Cancer Res. 55, 3752-3756, 1995

    被引用文献10件

  • <no title>

    MAEDA H.

    J. Controlled Release 65, 271-284, 2000

    被引用文献35件

  • Pharmacokinetics and Biodisposition of Poly(vinyl alcohol) in Rats and Mice

    KANEO Yoshiharu , HASHIHAMA Shiori , KAKINOKI Atsufumi , TANAKA Tetsuro , NAKANO Takayuki , IKEDA Yuka

    Drug metabolism and pharmacokinetics 20(6), 435-442, 2005-12-27

    J-STAGE 医中誌Web DOI 参考文献28件 被引用文献3件

  • <no title>

    BEAUCHAMP C. O.

    Anal. Biochem. 131, 25-33, 1983

    被引用文献4件

  • <no title>

    DOSIO F.

    J. Controlled Release 47, 293-304, 1997

    被引用文献1件

  • <no title>

    RINGEL I.

    J. Pharmacol. Exp. Ther. 242, 692-698, 1987

    被引用文献2件

  • Synthesis of Poly(vinyl alcohol)-Doxorubicin Conjugates Containing cis-Aconityl Acid-Cleavable Bond and Its Isomer Dependent Doxorubicin Release

    Kakinoki Atsufumi , Kaneo Yoshiharu , Ikeda Yuka , TANAKA Tetsuro , FUJITA Kahee

    Biological & pharmaceutical bulletin 31(1), 103-110, 2008-01-01

    機関リポジトリ J-STAGE DOI 参考文献33件 被引用文献1件

  • A PHARMACOKINETIC ANALYSIS PROGRAM (MULTI) FOR MICROCOMPUTER

    YAMAOKA K. , TANIGAWARA YUSUKE , NAKAGAWA TERUMICHI , UNO TOYOZO

    J. Pharmacobio-Dyn. 4, 879-885, 1981

    被引用文献90件

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 
ページトップへ