Pharmacodynamics Study of Paclitaxel-loaded Rhein Conjugate Micelles in Tumor-bearing Mice
OBJECTIVE To study the in vivo pharmacodynamics of paclitaxel-loaded TPGS-modified carboxymethyl chitosan-rhein conjugate micelles(PTX/TPGS-CR micelles)in tumor-bearing mice.METHODS The pH and osmotic pressure value of PTX/TPGS-CR micelles were determined.The 4T1 subcutaneous transplanted tumor model was established in Balb/c mice.Taxol ® was used as the positive control,and the tumor growth curve and tumor inhibition rate were used as the main indicators.The safety and effi-cacy of PTX/TPGS-CR micelles were investigated by observing the changes in body weight,organ index and pathological tissue sections of mice,and measuring the expression of P-gp protein in tumor tissues of each group.RESULTS The pH value was similar to that of 0.9％sodium chloride injection(5.0-7.0),and the osmotic pressure value was 736.6-757.2 kPa.The tumor inhibition rates of Taxol® and PTX/TPGS-CR micelle in low,medium and high dose groups were 29.91％,20.87％,41.06％and 41.84％,respec-tively.The antitumor effect of PTX/TPGS-CR micelles was better than that of Taxol ® at the same dose(P＜0.05),and showed a dose-dependent feature.During the administration period,the body weight and organ of the mice in the PTX/TPGS-CR micelle group at the same dose showed no significantly affected,indicating that PTX/TPGS-CR micelles had better safety.The results of P-gp expres-sion in tumor tissue showed that TPGS-CR micelles could inhibit the expression of P-gp protein.CONCLUSION PTX/TPGS-CR mi-celle preparation is a nano preparation with high efficiency and low toxicity.It has a good antitumor effect and can reduce the toxicity of PTX.Moreover,it can improve the sensitivity of tumor cells to PTX by inhibiting the expression of P-gp,which is conducive to the treatment of tumors.
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维普
