Objective: Three kinds of paclitaxel saturated fatty acid ester liposomes were prepared to preliminarily compare the difference between them in anti-tumor, and to explore the reasons for the difference of efficacy by the study of tissue distribution.Methods:Three kinds of paclitaxel fatty acid ester liposomes were prepared by thin film dispersion method, and the particle size, potential, encapsulation efficiency and drug loading were measured, respectively. A mouse model of breast cancer was established, and paclitaxel injection (Taxol), paclitaxel myristate liposome (PTX-MA-L), paclitaxel palmitate liposome (PTX-PA-L) and paclitaxel stearate liposome (PTX-SA-L) were injected via the tail vein, respectively. The anti-tumor effects of the two preparations were investigated, and the safety of the preparations was evaluated by routine blood tests. Finally, the prodrug metabolism for three prodrug liposomes was evaluated by in vivo tissue distribution.Results:Three taxol saturated fatty acid ester liposomes were successfully constructed. The particle sizes of PTX-MA-L, PTX-PA-L and PTX-SA-L are (69.56±1.08), (72±0.86) and (75±1.02) nm; Polymer dispersity index (PDI) are (0.185±0.009), (0.165±0.012), (0.171±0.024); Zeta potentials are -(11.26±1.37), -(12.18±1.86), -(13.92±0.59) mV, respectively. Encapsulation rates are (95±0.39)%, (97±0.28)% and (98±0.19)%, respectively. In pharmacodynamic evaluation in 4T1 breast cancer transplanted tumor model, the pharmacodynamic of PTX-PA-L at equal dose was stronger than that of taxol, PTX-MA-L and PTX-SA-L. The results of routine blood test showed that the blood cell level of paclitaxel fatty acid ester liposome was significantly higher than that of paclitaxel injection. The tissue distribution results showed that PTX-MA-L was metabolized to PTX at a fast rate, short half-life and fast elimination rate. PTX metabolized from PTX-PA-L increases slowly with time. Its half-life is the longest among the three prodrug liposomes, the area under the drug-time curve is the largest, and the clearance rate is the lowest. PTX-SA-L was metabolized to PTX the most slowly, and the maximum plasma concentration was the lowest in tumors.Conclusion:The paclitaxel prodrug liposome modified with saturated fatty acid has better tumor treatment effect and alleviates the toxic and side effects caused by traditional paclitaxel dosage forms. Among them, the antitumor effect of PTX-PA-L is better than that of PTX-MA-L and PTX-SA-L, which may be related to the metabolism of fatty acid prodrugs in vivo.