College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan 712-749, Republic of Korea.
College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, Republic of Korea.
Int J Pharm. 2020 May 30;582:119330. doi: 10.1016/j.ijpharm.2020.119330. Epub 2020 Apr 13.
The hindrances in achieving clinically translatable anticancer platforms are being tackled through nanotechnology-based formulations. In this study, stimuli-responsive, phytoactive constituent-loaded nanophytoliposomes were fabricated for designing a specific antitumor platform. Ursolic acid (UA)-loaded nanophytoliposomes (UA-PLL-HA.P) enwrapped in a poly-L-lysine (PLL) coat and hyaluronic acid (HA) were nanosized; these nanophytoliposomes had spherical morphology, slightly negative charge, and an in-range polydispersity index (~0.25). Successful fabrication of the nanosystem was proven through several characterization methods and the pH- and enzyme-responsiveness of the nanosystem was assessed through a release study. The cellular internalization in CD44 receptor-expressing cell lines was amplified by enhanced permeation and retention as well as by active targeting. In vitro antitumor behavior was confirmed through in vitro cytotoxic and apoptotic activity of the nanosystem. Similarly, in vivo imaging showed exceptional biodistribution in the tumor in agreement with the in vitro findings. Moreover, the tumor inhibitory rate of UA-PLL-HA.P was significantly higher, and was ascribed to the targeting potential and stimuli-responsiveness. In summary, UA-PLL-HA.P exhibited pronounced anticancer effect and could open a number of possibilities for discovering novel phytoconstituent-incorporated nanoformulations.
通过基于纳米技术的制剂来解决实现临床转化抗癌平台的障碍。在这项研究中，制备了响应刺激的、含有植物活性成分的纳米植物脂囊泡，用于设计特定的抗肿瘤平台。负载熊果酸（UA）的纳米植物脂囊泡（UA-PLL-HA.P）被包裹在聚-L-赖氨酸（PLL）涂层和透明质酸（HA）中，呈纳米尺寸；这些纳米植物脂囊泡具有球形形态、轻微的负电荷和适中的多分散指数（约 0.25）。通过多种表征方法证明了纳米系统的成功制备，并通过释放研究评估了纳米系统的 pH 和酶响应性。通过增强渗透和保留以及主动靶向作用，放大了在表达 CD44 受体的细胞系中的细胞内化。通过纳米系统的体外细胞毒性和细胞凋亡活性证实了其体外抗肿瘤行为。同样，体内成像显示了在肿瘤中的出色的生物分布，与体外发现一致。此外，UA-PLL-HA.P 的肿瘤抑制率显著更高，这归因于靶向潜力和刺激响应性。总之，UA-PLL-HA.P 表现出明显的抗癌作用，并为发现新型植物成分纳米制剂开辟了许多可能性。
