Pharmacodynamics Study Of Methotrexate Sustained-Release Implants In Sarcoma Bear Mice

Objective: In this study,methotrexate sustained-release implants were prepared.The degradation ration and cumulative release in vitro and in vivo of the implants were determined separately.The effect of methotrexate sustained-release implants on delayed sarcoma recurrence and inhibited tumor growth were investigated.Themethotrexate sustained-release implants made herein was compared with traditional delivery system to explore their superiority.Method: 1)PLGA and PEG4000 were used as excipients and hot-melting extrusion method was applied to fabricate methotrexate sustained-release implants,whose cumulative release ratio in vitro and in vivo were measured by UV and HPLC respectively.HPLC was also applied to determine the drug actual content.2)KM mice were inoculated subcutaneously with Sarcoma 180 cells at the axillary region for simulating postoperative residual lesions.Adjuvant chemotherapy after radical operation model was fabricated and the effect of local administration of methotrexate sustained-release implants on delayed sarcoma recurrence was evaluated.3)Sarcoma 180 cells were injected subcutaneously in the axilla of KM mice to establish the S180 sarcoma model.The methotrexate sustained-release implants was implanted at a predetermined time point to evaluate its antitumor efficiency.Results: Results demonstrated that drug actual contentwas up to8.34% ± 0.65 and was consistent with theoretical content.Methotrexate sustained-release implants can maintain a sustained and controlled release up to 7 d in vitro release and 15 d in vivo release respectively.Compared with traditional delivery system,methotrexate sustained-release implants we prepared were more effective in delaying tumor recurrence and prolonging the survival of mice.And the tumor growth inhibition rate of methotrexate sustained-release implants was as high as 77.06%,while that of methotrexate saline was only 30.15%.