ABSTRACT
OBJECTIVE: To prepare paclitaxel loaded D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)-modified carboxymethyl chitosan-rhein polymeric micelles (PTX/TPGS-CR PMs) and preliminarily evaluate their performance. METHODS: PTX/TPGS-CR PMs was prepared by dialysis method, and the preparation procedure of PTX/TPGS-CR PMs was optimized by single factor with the drug loading, encapsulation rate and particle size as the indicators, then the optimized preparation procedure was verified. The safety of PTX/TPGS-CR PMs was initially investigated by the hemolysis test and the vascular irritation test. The cytotoxicity of PTX/TPGS-CR PMs in Hela cells was studied by MTT assay. Cell uptake experiments were performed by laser confocal microscopy and flow cytometry to investigate the uptake of PTX/TPGS-CR PMs by Hela cells. RESULTS: The particle size and PDI of PTX/TPGS-CR PMs prepared by the optimized preparation were (197.3±4.4) nm and (0.131±0.021), respectively. The Zeta potential was (-31.8±0.5) mV. The drug loading and encapsulation efficiency were (48.20±3.03)% and (87.26±4.91)%, respectively. The hemolytic test results showed that the hemolysis rate was less than 1.71%. No obvious irritation was observed after intravenous injection. The cytotoxicity of PTX/TPGS-CR PMs in Hela cells was concentration-and time-dependent. Cell uptake experiments showed that PTX/TPGS-CR PMs could be efficiently uptake by Hela cells. CONCLUSION: The PTX/TPGS-CR PMs has high drug loading and encapsulation efficiency, good safety. And they exhibite slightly better antitumor activity in vitro than Taxol®.