Preparation of Paclitaxel Palmitate Liposomes and Preliminary Investigation of Its Pharmacodynamics and Safety / 中国药学杂志

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 tumorbearing 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.