Combination Effect of PEGylated Liposome Co-encapsulating Doxorubicin and Docetaxel in Murine Melanoma Cells

Aim and Background: The simultaneous delivery of more than one anti-tumor agent (combination therapy) through a Nano drug delivery system, such as liposomes, is a suitable way to bypass the significant drawbacks of chemotherapy. So in this study, we aimed to assay the combined cytotoxicity effect of doxorubicin and docetaxel in a PEGylated liposome against the murine melanoma cells, B16F10. Methods: The synergistic combination effect of free doxorubicin and docetaxel at varying dose ratios was examined using the MTT. The liposomal docetaxel (DTX-Lip), composed of HSPC/mPEG-DSPE/Cholesterol/DTX, was prepared by the passive loading method. Then, according to the synergistic ratio of the drugs, doxorubicin was added to the DTX-Lip through the remote loading method (DTX-DOX-Lip). The liposome s physical properties and the drugs encapsulation efficiency were also evaluated. The cytotoxicity effect of the prepared liposome was assessed by the MTT test, and its combination index was calculated by CalcuSyn software. Results and discussion: The synergistic ratio of doxorubicin: docetaxel was 1:2 and 1:10, with the combination index (CI) of 0.35 and 0.2, respectively. The mean particle size and zeta potential of DTX-DOX-Lip were (122±2) nm and (−8.73±0.35) mV, respectively. In addition, the encapsulation efficiency was 71% for doxorubicin and 62% for docetaxel. Moreover, DTX-DOX-Lip showed considerable cytotoxicity in B16f10 cells 48 hr post-treatment, with CI 0.4 and 0.135 for DTX-DOX-Lip (1:2) and DTX-DOX-Lip (1:10), respectively, showing the significant synergistic effect. Conclusion: The in vitro results of this study showed that the DTX-DOX-Lip is a useful approach for reducing the dose of drugs while increasing their toxicity effects. Actually, these findings point out the challenges to the design of synergistic treatment.