Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, PR China.
School of Pharmacy, Henan University of Traditional Chinese Medicine, Zhengzhou, PR China.
Drug Deliv. 2020 Dec;27(1):228-237. doi: 10.1080/10717544.2020.1716877.
Due to their various biological activities that are beneficial to human health and antitumor effect, flavonoid compounds have attracted much attention in recent years. Hydrous icaritin (HICT) was such a flavonoid that can inhibit the growth of breast cancer and cancer stem cells. In order to overcome the insolubility problem, HICT was fabricated into nanorods (NRs) through anti-solvent precipitation in this paper using D-α tocopherol acid polyethylene glycol succinate and sodium oleate as a co-stabilizer meanwhile using the mixture of ethanol and acetone (1:2, v/v) as the organic solvent. The obtained HICT NRs showed an average particle size 222.0 nm with a small polydispersity index value of 0.124 and a high zeta potential of - 49.5 mV. HICT NRs could maintain similar particle size in various physiological medium and could be directly lyophilized without the addition of any cytoprotectants and then reconstituted into a colloidal system of similar size. The resultant HICT NRs had a high drug loading content of 55.6% and released HICT in a steady and constant pattern. MTT assay indicated NRs enhanced HICT's antitumor activity to ninefold against MCF-7 breast carcinoma cells. studies demonstrated oral administration free HICT had almost no tumor inhibitory effect while HICT NRs showed a tumor inhibition rate of 47.8%. When intravenously injected, HICT NRs displayed similar therapeutic efficacy to paclitaxel injections (70.4% vs. 74.5%, TIR). This may be partly due to the high accumulation of the injected HICT NRs in tumor ranking only second to that in the liver but much higher than in other organs. These results demonstrated that HICT NRs could be a promising antitumor agent for the treatment of breast cancer in clinic.
由于其有益于人类健康和抗肿瘤的多种生物活性，近年来黄酮类化合物引起了广泛关注。水飞蓟素（HICT）是一种可以抑制乳腺癌和癌症干细胞生长的黄酮类化合物。为了克服其不溶性问题，本文采用醇/酮（1:2，v/v）混合有机溶剂，以 D-α-生育酚聚乙二醇琥珀酸酯和油酸钠为共稳定剂，通过反溶剂沉淀法将 HICT 制成纳米棒（NRs）。所得 HICT NRs 的平均粒径为 222.0nm，具有较小的多分散指数值（0.124）和较高的 zeta 电位（-49.5mV）。HICT NRs 在各种生理介质中能够保持相似的粒径，并且无需添加任何细胞保护剂即可直接冻干，然后再复溶成相似粒径的胶体体系。所得 HICT NRs 的载药量高达 55.6%，能够以稳定且持续的方式释放 HICT。MTT 试验表明，NRs 使 HICT 对 MCF-7 乳腺癌细胞的抗肿瘤活性增强了九倍。研究表明，口服游离 HICT 几乎没有肿瘤抑制作用，而 HICT NRs 则表现出 47.8%的肿瘤抑制率。静脉注射 HICT NRs 时，其治疗效果与紫杉醇注射液相似（70.4%对 74.5%，TIR）。这可能部分归因于注射的 HICT NRs 在肿瘤中的高蓄积率，仅次于肝脏，但远高于其他器官。这些结果表明，HICT NRs 可能成为治疗乳腺癌的一种有前途的抗肿瘤药物。
