Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Int J Pharm. 2023 Apr 5;636:122849. doi: 10.1016/j.ijpharm.2023.122849. Epub 2023 Mar 17.
Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/Combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential in synergistic cancer therapy. However, it is still unclear how the nanoparticles' formula, such as injection dose, active agent ratio, and drug loading content, affects the side effects and in vivo efficacy of CB-NPs. In this study, a series of CB-NPs with different BLZ945/CA4 (B/C) ratios and drug loading contents were synthesized and evaluated on a hepatoma (H22) tumor-bearing mice model. The injection dose and B/C ratio were found to have a significant influence on the in vivo anticancer efficacy. The CB-NPs 20 with B/C weight ratio of 0.45/1, and total drug loading content (B + C) of 20.7 wt%, showed the highest potential for clinical application. Systematic pharmacokinetics, biodistribution, and in vivo efficacy evaluation for CB-NPs 20 have been finished, which may provide significant instruction for medicine screening and clinical application.
聚（L-谷氨酸）-g-甲氧基聚（乙二醇）/康普瑞汀 A4（CA4）/BLZ945 纳米粒（CB-NPs）在协同癌症治疗中显示出巨大的潜力。然而，纳米粒的配方，如注射剂量、活性剂比例和载药含量如何影响 CB-NPs 的副作用和体内疗效，目前仍不清楚。在本研究中，我们合成了一系列具有不同 BLZ945/CA4（B/C）比例和载药含量的 CB-NPs，并在肝癌（H22）荷瘤小鼠模型上进行了评价。结果发现，注射剂量和 B/C 比值对体内抗癌疗效有显著影响。B/C 重量比为 0.45/1，总载药含量（B+C）为 20.7wt%的 CB-NPs 20 具有最高的临床应用潜力。我们已经完成了 CB-NPs 20 的系统药代动力学、生物分布和体内疗效评价，这可能为药物筛选和临床应用提供重要指导。
