In Vitro Release and Anti-Tumor Studies of Paclitaxel-Loaded Rhein Conjugate Micelles
OBJECTIVE To study the in vitro release behavior and anti-tumor effect of paclitaxel-loaded rhein conjugate(PTX/TPGS-CR)micelles.METHODS The in vitro drug release behavior of PTX/TPGS-CR micelles in different release media was inves-tigated by dialysis method with Taxol ® as the control.The cytotoxicity of PTX/TPGS-CR micelles on mouse breast cancer 4T1 cells was evaluated by MTT assay with Taxol ® as a control.The effect of PTX/TPGS-CR micelles on the cell cycle and apoptosis of human cervical carcinoma HeLa cells was detected by flow cytometry.The effect of PTX/TPGS-CR micelles on the migration of HeLa and 4T1 cells was investigated by scratch experiments.RESULTS The results of in vitro release assay showed that 50.84％and 71.38％of PTX in PTX/TPGS-CR micelles were released in pH 7.4 phosphate buffer(PBS)within 12 and 72 h,respectively,79.19％of PTX in PTX/TPGS-CR micelles were released in pH 5.8 PBS which simulated the tumor microenvironment within 12 h,and almost all of PTX in the micelles was released within 72 h.The results of the cytotoxicity assay showed that PTX/TPGS-CR micelles had a strong in-hibitory effect on the proliferation of 4T1 cells and displayed a time-and-concentration-dependent characteristic,with IC50 of 0.321 9 nmol·mL-1 at 72 h.PTX/TPGS-CR micelles could induce early apoptosis and late apoptosis in HeLa and 4T1 cells.PTX/TPGS-CR micelles can induce HeLa cells arrest in G2/M phase(arrested by PTX)and GO/G1 phase,which inhibited cell division and prolifera-tion.PTX/TPGS-CR micelles can inhibit the migration of HeLa and 4T1 cells and reduce tumor metastasis.CONCLUSION PTX/TPGS-CR micelles have good pH-responsive drug release characteristics,which can release drugs slowly in the blood environment and rapidly in the tumor microenvironment.PTX/TPGS-CR micelles could inhibit tumor cells proliferation and migration and promote cell apoptosis.PTX/TPGS-CR micelles have a good tumor treatment potential.
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