Preparation of liposomal paclitaxel and its toxicity and antitumor effect / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare the paclitaxel liposomes and evaluate its physicochemical property, toxicity and pharmacodynamics. METHODS: SPC, mPEG2000-DSPE and paclitaxel were dissolved in chloroform in a mole ratio of 1000.55. Oil phase and water phase were mixed and skived. The emulsion was homogenized to form liposomes. The mean diameter of liposomes was determined by dynamic light scattering (DLS) techniques. Low-speed centrifugation was employed to determine encapsulation efficiency (EE). The maximum tolerated doses (MTD) was determined in normal KM mice, and antitumor effect was evaluated in H22/KM mice xenograft tumor model. RESULTS: The mean diameter of paclitaxel liposomes was (140±10) nm. The EE was over 95% when the molar ratio of paclitaxel to SPC ranged from 3% to 6%. The MTDs of Pac-lipo and Pac-free in male KM mice were 64.8 and 29.4 mg · kg-1, respectively. Pac-lipo inhibited H22tumor weight dose-dependently. CONCLUSION: Pac-lipo had a high EE, and could increase the therapeutic index significantly, compared with Pac-free.