In Vivo Pharmacodynamics and Safety Evaluation of Lactose-Doxorubicin Drug-Drug Conjugate Nanomicelle / 中国药学杂志

ABSTRACT

OBJECTIVE: The lactose-doxorubicin amphiphilic small molecule nanomicelles and evaluate its liver cancer targeting and antitumor efficacy and safety in vivo. METHODS: Lactose-doxorubicin nanomicelles (Lac-DOX NMs) were prepared by thin film hydration method. The particle size was determined by dynamic light scattering and observed by transmission electron microscopy. The effect of Lac-DOX NMs on the targeting of tumor cell was investigated by cell uptake experiments.Cytotoxicity of nanomicelles and free doxorubicin were evaluated by CCK-8 assay.The subcutaneous xenograft model of BALB/c-nu mice was constructed to investigate the anti-tumor effect of Lac-DOX NMs; the effect of the preparation on liver function of mice was examined by blood biochemical test to evaluate the safety of the preparation.RESULTS: Lac-DOX NMs were successfully prepared with a particle size of (169.2±0.9) nm. Cellular uptake experiments indicated that Lac-DOX NMs are targeted to HuH-7 hepatoma cells.The IC50 of nanomicelle and free DOX were 3.596 and 2.131 μg•mL-1, respectively. The results of pharmacodynamic experiments showed that Lac-DOX NMs could significantly inhibit the growth of transplanted tumors in mice. The tumor inhibition rates of high and low doses of Lac-DOX NMs were 69.72% and 52.40%, respectively, which were higher than those of free DOX (52.27%). P values are 0.000 16 and 0.94. CONCLUSION: Modification of doxorubicin with lactose and its preparation into nanometer preparations can significantly improve the targeting of doxorubicin to liver cancer cells, enhance the anti-tumor effect, reduce the side effects of doxorubicin, and improve the safety of medication.