Water-soluble taxol conjugates with dextran and targets tumor cells by folic acid immobilization.
BACKGROUND
Paclitaxel (taxol) is a very effective anticancer drug. However, the solution used to enhance the water solubility of paclitaxel, a mixture of polyoxyethylene castor oil (Cremphor EL) and dehydrated ethanol, causes irritation. Our aim is to develop a water-soluble taxol with a high anticancer effect.


METHODS
Taxol derivatives (conjugation with aminated dextran, Dex-TXL) were synthesized for the water-solublization of taxol and folic acid (FA) was ionically and covalently conjugated with Dex-TXL. In addition, their anticancer activity was investigated in vitro with KB cells (a folate receptor-overexpressing carcinoma cell line of the oral cavity).


RESULTS
The high solubility of Dex-TXL conjugates (2700 times higher than that of intact taxol) needed no additional Cremophor EL or dehydrated ethanol. Dex-TXL showed 2-3 times greater anticancer effect when conjugated with FA.


CONCLUSIONS
These results suggest that conjugation with dextran and FA could bring about an improvement in taxol anticancer therapy.
Nakamura
Junichi
J
Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Nakajima
Naoki
N
Matsumura
Kazuaki
K
Hyon
Suong-Hyu
SH
D000327:Adsorption; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry* / Q000493:pharmacokinetics; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D007624:KB Cells; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D012995:Solubility; D014867:Water / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; D003911:Dextrans; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D014867:Water; D005492:Folic Acid; D017239:Paclitaxel