Annonaceous acetogenins (ACGs) nanosuspensions based on a self-assembly stabilizer and the significantly improved anti-tumor efficacy
Annonaceous acetogenins (ACGs) nanosuspensions based on a self-assembly stabilizer and the significantly improved anti-tumor efficacy
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DOI：
10.1016/j.colsurfb.2016.05.012
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发表时间：
2016-09-01
影响因子：
5.8
通讯作者：
Wang, Xiangtao
中科院分区：
文献类型：
--
作者：
Hong, Jingyi;Li, Yanhong;Wang, Xiangtao
Annonaceous acetogenins (ACG) 对多种癌症表现出抗肿瘤活性。然而，这些物质的溶解度较差，限制了临床应用。在这项研究中，羟丙基-β-环糊精（HP-β-CD）和大豆卵磷脂（SPC）自组装成两亲性复合物。使用该复合物作为稳定剂，制备出平均粒径为 144.4 nm、zeta 电位为-22.9 mV、药物有效负载为 46.17% 的 ACGs 纳米混悬剂（ACGs-NSps）。 ACGs-NSps在体外表现出缓释性，在血浆和模拟胃肠液中具有良好的稳定性，满足静脉注射和口服给药的需求。与溶液中的 ACG 相比，ACGs-NSps 对 Hela 和 HepG2 癌细胞系的细胞毒性显着增加（体外细胞毒性测定）。对携带 H22 肿瘤的小鼠进行的体内研究表明，纳米悬浮液显着提高了 ACG 的抗肿瘤活性。口服给药时，ACGs-NSps 在油溶液中 ACGs 剂量的 1/10 下实现了类似的肿瘤抑制率（47.94% vs. 49.74%，p > 0.05）。当将ACGs-NSps静脉注射到小鼠体内时，进一步提高了治疗效果（70.31%）。借助纳米混悬剂技术，ACGs可能成为临床使用的有效抗肿瘤药物。 (C) 2016 Elsevier B.V. 保留所有权利。
Annonaceous acetogenins (ACGs) have exhibited antitumor activity against various cancers. However, these substances' poor solubility has limited clinical applications. In this study, hydroxypropyl-betacyclodextrin (HP-beta-CD) and soybean lecithin (SPC) were self-assembled into an amphiphilic complex. ACGs nanosuspensions (ACGs-NSps) were prepared with a mean particle size of 144.4 nm, a zeta potential of -22.9 mV and a high drug payload of 46.17% using this complex as stabilizer. The ACGs-NSps demonstrated sustained release in vitro and good stability in plasma as well as simulated gastrointestinal fluid, and met the demand of both intravenous injection and oral administration. The ACGs-NSps demonstrated significantly increased cytotoxicity against Hela and HepG2 cancer cell lines compared to ACGs in solution (in vitro cytotoxicity assay). An in vivo study with H22-tumor bearing mice demonstrated that nanosuspensions significantly improved ACGs' antitumor activity. When orally administered, ACGs-NSps achieved a similar tumor inhibition rate at 1/10th the dose of ACGs in an oil solution (47.94% vs. 49.74%, p > 0.05). Improved therapeutic efficacy was further achieved when the ACGs-NSps were intravenously injected into mice (70.31%). With the help of nanosuspension technology, ACGs may be an effective antitumor drug for clinic use. (C) 2016 Elsevier B.V. All rights reserved.