Preparation and Cytotoxicity Evaluation of Doxorubicin-loaded Rhein Conjugate Micelles

OBJECTIVE To prepare doxorubicin(DOX)-loaded TPGS modified carboxymethyl chitosan-rhein(TPGS-CR) polymeric micelles(DOX/TPGS-CR PMs), and study its cytotoxicity in human breast cancer MCF-7 cells in vitro. METHODS DOX/TPGS-CR PMs were prepared by dialysis method using TPGS-CR conjugate. The particle size of DOX/TPGS-CR PMs was detected by dynamic light scattering(DLS), the entrapment efficiency(EE) and the drug loading-capacity(DL) were studied by Ultraviolet spectrophotometry. The vitro release studies were performed in PBS(pH 7.4), the cumulative release rate of DOX was calculated, and the cumulative release profile was plotted. The cytotoxicity of DOX/TPGS-CR PMs in human breast cancer MCF-7 cells was detected by MTT assay, and the survival rate of the cells was calculated. RESULTS The average particle size and polydispersity coefficient of DOX/TPGS-CR PMs were (151.3±1.8)nm and 0.129±0.020, respectively. The zeta potential of DOX/TPGS-CR PMs was(-26.9±0.8)mV. The DL and EE of DOX/TPGS-CR PMs were(23.16±0.01)% and(55.00±0.04)%, respectively. Cumulative release of DOX in PBS(pH 7.4) from DOX/TPGS-CR PMs was only about(35.73±2.21)% at 24 h, while the cumulative release of free DOX·HCl reached(90.25±6.20)% at 6 h. The cytotoxicity of DOX/TPGS-CR PMs was better than doxorubicin hydrochloride(DOX·HCl) in the concentration range of 5-20 μg·mL^-1, especially at 48 h. CONCLUSION The DL of DOX/TPGS-CR PMs is good, and the particle size is small and uniform. DOX/TPGS-CR PMs have a sustained-release characteristic. TPGS-CR conjuage is less toxic and safe. DOX/TPGS-CR PMs display cytotoxicity significantly in MCF-7 cells.