Synthesis and In vitro cytotoxicity of poly(ethylene glycol)–epothilone B conjugates |
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Authors: | Haiyan Zhang Kun Wang Xiaochen Cheng Yuxin Lu Qinglin Zhang |
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Affiliation: | 1. School of Pharmacy, Central South University, Changsha, People's Republic of China;2. Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, People's Republic of China |
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Abstract: | Natural epothilone B (EPOB) is currently in clinical trials for treatment of advanced cancers. In this study, two poly(ethylene glycol) (PEG)–EPOB conjugates were synthesized with carbodiimide chemistry with linear PEG Methoxy‐PEG‐Carboxymethy(mPEG‐COOH) with different molecular weights (5 and 20 kDa). The products were confirmed by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy and 1H‐NMR, which showed that PEGylation only took place at the 7‐OH site of EPOB. The solubilities of PEG5K–EPOB the conjugate of mPEG‐COOH (MW 5,000) and epothilone B and PEG20K–EPOB the conjugate of mPEG‐COOH (MW 20,000) and epothilone B were determined to be 4.93 × 10?2 and 1.58 × 10?2 mmol/mL; this showed improvements of 35 and 11 times, respectively, over that of free EPOB (1.4 × 10?3 mmol/mL). Moreover, the conjugates were more stable than that of free EPOB in plasma. The cytotoxicity of conjugates was evaluated on human breast cancer MCF‐7 cells with an 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide(MTT) based assay. The half maximal inhibitory concentration of a substance(IC50) values of EPOB, PEG5K–EPOB, and PEG20K–EPOB were 6.0 × 10?4, 0.57, and 8.4 × 10?3 μM, respectively. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41123. |
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Keywords: | applications drug‐delivery systems processing and synthesis |
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