Investigation on Biodistribution of Mitoxantrone-Insulin Conjugates in vivo and Pharmacodynamics in

OBJECTIVE To investigate the initiative target efficiency of newly conjugated mitoxantrone-insulin (MIT-INS) on tumor in vivo and in vitro.METHODS The drug biodistributions of mitoxantrone (MIT) and MIT-INS in vivo were examined in tumor-bearing mice, while MTT assays were employed to evaluate the depression efficiencies of MIT-INS and MIT on SMMC-7721 hepatocarcinoma cells in vit-ro .RESULTS It was proved in vivo that,compared with MIT,the half-life of MIT-INS was prolonged by 75% ; the area under the concentration-time curve (AUC) of MIT-INS was enlarged by 67% ; the initial concentration of MIT-INS was increased by almost 100% ; the relative target efficiency (RTE) of MIT-INS was 1.67; and MIT concentrations of MIT-INS were much lower in all examined organs, especially in heart. Moreover,the inhibition rate (IR) of MIT-INS, proved in vitro,was similar to that of the free drug.CONCLUSION MIT-INS has tumor-targeting property with enough anti-tumor activity, and insulin,as the vector of anti-tumor drugs,can improve target effect with low side effect.