The reversal of tumor drug resistance by liposomes containing docetaxel and verapamil / 药学学报

ABSTRACT

To study the reversal effect of docetaxel (DTX) and verapamil (VRP) liposome (DTX-VRP LP) on multidrug resistance of human breast cancer chemotherapy, DTX-VRP LP was prepared by thin film dispersion method. The particle size and zeta potential were measured by laser particle sizer. The drug loading, entrapment efficiency and the cumulative release rate of liposomes in phosphate buffer saline solution (PBS) with pH 7.4 and 6.8 were determined by ultrafiltration and dynamic dialysis, respectively. With DTX resistant human breast cancer cells (MCF-7/DTX) to study on the pharmacodynamics of liposomes in vitro and in vivo. The animal experiments were approved by the Animal Research Ethics Committee of School of Medicine of Shanghai Jiao Tong University (No. 2019-06-172). The average particle size and zeta potential of DTX-VRP LP were about 140.9 nm and -28.7 mV, respectively. The entrapment efficiency and drug loading of DTX and VRP in DTX-VRP LP were (81.7 ± 3.9)%, (2.9 ± 0.3)% and (59.6 ± 0.6)%, (1.6 ± 0.5)%, respectively. The cumulative release rate of the group of DTX-VRP LP was about 40% and 70% within 0-4 h in pH 7.4 and 6.8 PBS, respectively. It was slightly slower compared with other experimental groups. In vitro pharmacodynamics experiments, the value of IC50 of DTX solution, DTX LP and DTX-VRP LP were 3.19 ± 0.6, 1.46 ± 0.48 and 1.12 ± 0.33 μmol·L-1 on human breast cancer cells (MCF-7), respectively. The results showed the data was not much difference between the other groups and all experimental groups had strong cytotoxicity on MCF-7. However, on the MCF-7/DTX, the IC50 values of the other groups were greater than 10 μmol·L-1 while DTX-VRP LP group 7.4 ± 2.86 μmol·L-1. The results showed DTX-VRP LP had obvious cytotoxicity with the concentration dependent reversal of multidrug resistance (MDR) of breast cancer MCF-7/DTX cells (P<0.05), the other experimental groups had no effect on MCF-7/DTX cells. The inhibitory effect of MCF-7/DTX in vivo is consistent with that in vitro. In conclusion, DTX-VRP LP could reverse the MDR of MCF-7/DTX cells.