Luo Mei, Sun Huiwei, Jiang Qiyu, Chai Yantao, Li Congshu, Yang Bin, Hong Zhixian
Institute of Life Sciences, Jinzhou Medical University, Jinzhou, China.
Department of Infectious Disease, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
Front Oncol. 2021 Dec 2;11:777356. doi: 10.3389/fonc.2021.777356. eCollection 2021.
The molecularly targeted agent anlotinib offers a novel therapeutic strategy against advanced hepatocellular carcinoma (HCC). With this study, we aimed to solve the technical problem of anlotinib being insoluble in injectable solutions; we also aimed to assess the antitumor activity of anlotinib on hepatocellular carcinoma cells. We prepared an anlotinib nanocrystal injection by wet grinding, and we optimized the prescription process using a transmission electron microscope (TEM) and a laser particle size analyzer (LPSA). The release of anlotinib from the injected nanocrystals was evaluated using LC-MS/MS , and the drug's anti-tumor effects were assessed in a nude mice tumor model. The anlotinib nanocrystals had a uniform particle size distribution (the average nanoparticle size was ~200 nm). The preparation of anlotinib into nanocrystals did not change the original crystal structure. The intravenous injection of anlotinib nanocrystals achieved anti-tumor activity at very low doses compared to those required for oral administration of an anlotinib suspension: anlotinib nanocrystals at a dose of 50 μg/kg inhibited the subcutaneous growth of the HCC cell line MHCC97-H; whereas the dose of anlotinib suspension required for an equivalent effect was 1 mg/kg. Therefore, our novel anlotinib nanocrystal injection preparation provides an option for achieving a safe and effective molecularly targeted therapy against advanced HCC.
分子靶向药物安罗替尼为晚期肝细胞癌（HCC）提供了一种新的治疗策略。通过本研究，我们旨在解决安罗替尼不溶于注射剂的技术问题；我们还旨在评估安罗替尼对肝癌细胞的抗肿瘤活性。我们通过湿磨法制备了安罗替尼纳米晶体注射液，并使用透射电子显微镜（TEM）和激光粒度分析仪（LPSA）优化了处方工艺。使用LC-MS/MS评估安罗替尼从注射纳米晶体中的释放情况，并在裸鼠肿瘤模型中评估该药物的抗肿瘤效果。安罗替尼纳米晶体具有均匀的粒径分布（平均纳米粒径约为200nm）。将安罗替尼制备成纳米晶体并未改变其原始晶体结构。与口服安罗替尼混悬液所需剂量相比，静脉注射安罗替尼纳米晶体在极低剂量下即可实现抗肿瘤活性：50μg/kg剂量的安罗替尼纳米晶体可抑制肝癌细胞系MHCC97-H的皮下生长；而产生同等效果所需的安罗替尼混悬液剂量为1mg/kg。因此，我们新型的安罗替尼纳米晶体注射制剂为晚期HCC的安全有效分子靶向治疗提供了一种选择。
