Ao Hui, Lu Likang, Li Manzhen, Han Meihua, Guo Yifei, Wang Xiangtao
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, China.
Pharmaceutics. 2022 Jun 10;14(6):1232. doi: 10.3390/pharmaceutics14061232.
Annona squamosa seed oil (ASSO), which is a waste product in the extraction of annonaceous acetogenins (ACGs), displays good antitumor activity against a variety of tumor cells. However, ASSO is insoluble and has low bioavailability. In order to improve the solubility and application value of ASSO, the seed oil nanoparticles (ASSO-NPs) were successfully prepared only using TPGS as a stabilizer. ASSO-NPs obtained were spherical with a uniform size (less than 200 nm). ASSO-NPs showed the good storage stability at 25 ± 2 °C and were suitable for both oral administration and intravenous injection. The antitumor study in vitro and in vivo demonstrated more enhanced antitumor efficacy of ASSO-NPs than free ASSO. The ASSO-NPs group (15 mg/kg) had the highest tumor inhibition rate (TIR) of 69.8%, greater than the ASSO solution (52.7%, 135 mg/kg, p < 0.05) in 4T1 tumor-bearing mice. The in vivo biodistribution data displayed that the fluorescence intensity of ASSO/DiR-NPs in tumor was similar to that in liver in the presence of the reticuloendothelial system. Besides, the relative tumor-targeting index (RTTI) of (ACGs + ASSO)-NPs was 1.47-fold that of ACGs delivered alone, and there is great potential in ASSO-NPs as tumor-targeted delivery vehicles. In this study, ASSO-NPs were firstly prepared by a very simple method with fewer excipients, which improved the solubility and antitumor activity of the ASSO, displaying a good prospect in the in vivo delivery of natural bioactive compounds.
番荔枝种子油（ASSO）是从番荔枝素（ACGs）提取过程中产生的一种废弃物，对多种肿瘤细胞具有良好的抗肿瘤活性。然而，ASSO不溶于水且生物利用度低。为了提高ASSO的溶解度和应用价值，仅使用TPGS作为稳定剂成功制备了种子油纳米粒（ASSO-NPs）。所制备的ASSO-NPs呈球形，尺寸均匀（小于200nm）。ASSO-NPs在25±2℃下具有良好的储存稳定性，适用于口服给药和静脉注射。体内外抗肿瘤研究表明，ASSO-NPs的抗肿瘤效果比游离ASSO更强。在4T1荷瘤小鼠中，ASSO-NPs组（15mg/kg）的肿瘤抑制率（TIR）最高，为69.8%，高于ASSO溶液组（52.7%，135mg/kg，p<0.05）。体内生物分布数据显示，在存在网状内皮系统的情况下，ASSO/DiR-NPs在肿瘤中的荧光强度与在肝脏中的相似。此外，（ACGs+ASSO）-NPs的相对肿瘤靶向指数（RTTI）是单独递送ACGs的1.47倍，ASSO-NPs作为肿瘤靶向递送载体具有很大潜力。在本研究中，首次通过一种非常简单的方法，使用较少的辅料制备了ASSO-NPs，提高了ASSO的溶解度和抗肿瘤活性，在天然生物活性化合物的体内递送方面展现出良好的前景。
