| 論文名 |
Design and evaluation of folate-appended α-, β-, and γ-cyclodextrins having a caproic acid as a tumor selective antitumor drug carrier in vitro and in vivo. |
| 著者 |
Ayaka Okamatsu
Keiichi Motoyama
Risako Onodera
Taishi Higashi
Takahiro Koshigoe
Yasutaka Shimada
Kenjiro Hattori
Tomoko Takeuchi
Hidetoshi Arima
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| キーワード |
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| 出版年月 |
1970年1月 |
| 発表先 |
Biomacromolecules. 2013 Dec 9;14(12):4420-8. |
| WEBサイト |
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| 論文概要（和文） |
インビトロおよびインビボでの腫瘍選択的抗腫瘍薬物担体としてカプロン酸を有する葉酸付加α-、β-、およびγ-シクロデキストリンの設計および評価。 |
| 論文概要（英文） |
We reported that per-6-folic acid (FA)-appended β-cyclodextrin (β-CyD) possessing two caproic acids between FA and a β-CyD molecule as a spacer (Fol-c2-β-CyD) could be useful as a promising antitumor drug carrier. However, the effects of the cavity size and the spacer length on the carrier ability are not still known. In this study, we designed and evaluated the FA-appended three kinds of CyDs possessing a caproic acid as a spacer between FA and a CyD molecule (Fol-c1-CyDs) as a tumor targeting carrier for antitumor drugs. The stability constant of the Fol-c1-β-CyD/doxorubicin (DOX) complex was much higher than those of Fol-c1-α-CyD and Fol-c1-γ-CyD at pH 7.3. Antitumor activity of DOX was increased by the complexation with Fol-c1-β-CyD, but not with Fol-c1-α-CyD or Fol-c1-γ-CyD in KB cells, a folate receptor-α-positive cell line. Also, Fol-c1-β-CyD increased antitumor activities of paclitaxel and vinblastine, but not 5-fluorouracil. Furthermore, Fol-c1-β-CyD accelerated cellular uptake of DOX and inhibited its efflux from KB cells. The Fol-c1-β-CyD/DOX complex showed much higher antitumor activity than DOX alone after intratumoral and intravenous administrations to tumor-bearing mice with a negligible change of the blood chemistry values. These findings suggest that Fol-c1-β-CyD could be useful as a tumor-selective carrier for antitumor drugs. |
