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. MATERIALS AND 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. CONCLUSION: These results suggest that conjugation with dextran and FA could bring about an improvement in taxol anticancer therapy.
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. MATERIALS AND 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. CONCLUSION: These results suggest that conjugation with dextran and FA could bring about an improvement in taxol anticancer therapy.
Authors: Shiyi Zhang; Jiong Zou; Mahmoud Elsabahy; Amolkumar Karwa; Ang Li; Dennis A Moore; Richard B Dorshow; Karen L Wooley Journal: Chem Sci Date: 2013 Impact factor: 9.825