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- Title
Synthesis, Biological Evaluation and Low-Toxic Formulation Development of Glycosylated Paclitaxel Prodrugs.
- Authors
Mao, Yukang; Zhang, Yili; Luo, Zheng; Zhan, Ruoting; Xu, Hui; Chen, Weiwen; Huang, Huicai
- Abstract
Paclitaxel (PTX) is a famous anti-cancer drug with poor aqueous solubility. In clinical practices, Cremophor EL (polyethoxylated castor oil), a toxic surfactant, is used for dissolution of PTX, which accounts for serious side effects. In the present study, a single glucose-conjugated PTX prodrug (SG-PTX) and a double glucose-conjugated PTX prodrug (DG-PTX) were synthesized with a glycosylated strategy via succinate linkers. Both of the two prodrugs presented significant solubility improvement and drug-like lipophilicities. Compared to DG-PTX, SG-PTX manifested more promising release of the parent drug in serum. A high percentage of PTX released from SG-PTX could be detected after enzymatic hydrolysis of β-glucuronidase. Besides, both of the two prodrugs exhibited effective cytotoxicity against breast cancer cells and ovarian cancer cells, but presented reduced cytotoxicity against normal breast cells. Moreover, SG-PTX manifested impressive solubility in a low toxic formulation (without ethanol) with a different percentage of Cremophor EL. These results indicated that glycosylation is a promising strategy for PTX modification and SG-PTX may be a feasible and potential type of PTX prodrug. In addition, ethanol-free formulation with a low percentage of Cremophor EL might have the potential to develop a safer formulation for further studies of glycosylated PTX prodrugs.
- Subjects
PACLITAXEL synthesis; ANTINEOPLASTIC agents; PRODRUGS; DRUG side effects; CELL-mediated cytotoxicity
- Publication
Molecules, 2018, Vol 23, Issue 12, p3211
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules23123211