Preparation of Paclitaxel Palmitate Liposomes and Preliminary Investigation of Its Pharmacodynamics and Safety
CHENG Dan1, YU Nong2, XU You-fa2, FU Zhi-qin2, CHEN Jian-ming1,2,3*
1. School of Pharmacy, The Second Military Medical University, Shanghai 200433, China; 2. School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China; 3. Tasly Group Co. Ltd., Tianjin 300402,China
Abstract��OBJECTIVE To synthesize a prodrug of paclitaxel which is modified by palmitic acid at the 2��-hydroxyl position and prepare paclitaxel palmitate liposomes(PTX-PA-L), and then compare the pharmacodynamics and safety of PTX-PA-L in S180 tumor-bearing rats with paclitaxel injection. METHODS The derivative of paclitaxel was synthesized using 4-dimethylaminopyridine(DMAP) as acid binding agent and 1-(3-dimethylaminopropyl)-3-ethylenediamine(EDC) as dehydrating agent. PTX-PA was characterized by mass spectrometry and nuclear magnetic resonance spectroscopy(600 MHz 1H-NMR). PTX-PA-L were prepared using film dispersion-ultrasonic method. The particlesize and Zeta potential were measured using Malvern Zeta-sizer Nano S and the morphologywas characterized by TEM. The S180 sarcoma model in ICR mice was established to study the antitumor efficiency of PTX-PA-L in vivo. The hematological toxicity and body weight change of the mice were evaluated to study the safety of PTX-PA-L. RESULTS The prodrug PTX-PA was synthesized successfully. The liposomes had good morphological characteristics and light blue opalescence and the particle size was(104.82��1.23) nm. The pharmacodynamic study showed that compared with paclitaxel injection, PTX-PA-L had better antitumor efficacy on S180 tumor-bearing mice and the blood index indicated less decrease of white blood cells and neutrophils. CONCLUSION PTX-PA-L can improve the antitumor efficacy significantly and reduce the toxicity of paclitaxel injection.
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CHENG Dan, YU Nong, XU You-fa, FU Zhi-qin, CHEN Jian-ming. Preparation of Paclitaxel Palmitate Liposomes and Preliminary Investigation of Its Pharmacodynamics and Safety. Chinese Pharmaceutical Journal, 2018, 53(8): 614-619.
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2018, Vol. 53 
