Wang Ruyi, Xiao Yuxiao, Zhang Zhongtao, Huang Xiaoxian, Zhu Wanfang, Ma Xiao, Feng Feng, Liu Wenyuan, Han Lingfei, Qu Wei
Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 210009, China.
Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, China.
Adv Healthc Mater. 2024 Dec;13(31):e2401950. doi: 10.1002/adhm.202401950. Epub 2024 Sep 14.
Poor in vivo characteristics of gambogic acid (GA) and difficulties in industrial manufacturing of its nanocarriers have hindered its clinical translation. Therefore, a reproducible nano-drug delivery system must be developed to realize simpler manufacture and address inherent defects of GA, such as short circulation and severe side effects, in order to facilitate its clinical application. Herein, a drug self-assembled nanoparticles (NPs) consisting of a hydrophobic prodrug based on GA and oleyl alcohol (OA), as well as vitamin E-polyethylene glycol succinate (TPGS) as a shield to improve the stability of the NPs is reported. The preparation method is simple enough to stably facilitate large-scale manufacturing. The self-assembled NPs exhibit a remarkably high drug-loading capacity, and their prolonged circulation enables the NPs to demonstrate superior antitumor efficacy in both cellular and animal models. The flexible hydrophobic long chain wraps GA groups, which mitigates vascular irritation and reduces hemolysis rates. Consequently, the prodrug nano-system addresses GA-related concerns regarding stability, efficacy, and safety, offering a simple, stable, and secure nano-platform for similar candidate drugs.
藤黄酸（GA）较差的体内特性及其纳米载体在工业生产上的困难阻碍了其临床转化。因此，必须开发一种可重现的纳米药物递送系统，以实现更简便的生产，并解决GA的固有缺陷，如循环时间短和副作用严重等问题，从而促进其临床应用。在此，报道了一种由基于GA的疏水性前药和油醇（OA）组成的药物自组装纳米颗粒（NPs），以及作为稳定剂以提高NPs稳定性的维生素E - 聚乙二醇琥珀酸酯（TPGS）。该制备方法足够简单，能够稳定地促进大规模生产。自组装的NPs表现出极高的载药量，其延长的循环时间使NPs在细胞和动物模型中均表现出优异的抗肿瘤疗效。柔性疏水长链包裹GA基团，减轻了血管刺激并降低了溶血率。因此，前药纳米系统解决了与GA相关的稳定性、疗效和安全性问题，为类似候选药物提供了一个简单、稳定且安全的纳米平台。
