Wei-Ze Li, Wen-Xia Han, Ning Zhao, Shu-Miao He, Fei Liang, Li-Na Fu, Zhan-Rui Zhang, Xi-Feng Zhai, Li-Bin Yang
College of Pharmacy, Xi'an Medical University, Xi'an 710021, PR China.
College of Medical Technology, Xi'an Medical University, Xi'an 710021, PR China.
Eur J Pharm Sci. 2020 Oct 1;153:105496. doi: 10.1016/j.ejps.2020.105496. Epub 2020 Jul 28.
In this work, a novel embolic microspheres with micro nano binary progressive structure (MN-Ms) were developed for transarterial chemoembolization (TCE) applications. The Bletilla striata polysaccharide (Bsp) polymer can inhibit neovascularization and having a dimensional porous network structure, which as the first level of micron structure (microspheres) and will play a role on tumor embolization and inhibition of ischemia-induced neovascularization. The nano flexible liposomes which were embedded by the Bsp polymer microspheres as the second level nano structure to deliver drug across biological membrane barriers. And the micro nano binary progressive structure of MN-Ms was easily formed by using an emulsion crosslinking method. The MN-Ms appeared as perfect round shape with desired swelling and suspensibility characteristics, this was very convenient for embolizing operation by TCE. Due to the binary progressive structure, the MN-Ms could effectively site-specific delivery drug to the targeted liver tissue by enhancing the permeability of Sodium dimethyl-cantharidate (SC) across vessel walls & tissue matrix and delaying drug release at the site of administration, this caused the administrated SC mostly accumulated in the liver, also a higher cytotoxicity to human hepatoma cells. This work indicate that the MN-Ms may be a promising embolic agent for TCE applications for advanced liver cancer.
在这项工作中,开发了一种具有微纳二元递进结构的新型栓塞微球(MN-Ms)用于经动脉化疗栓塞(TCE)应用。白芨多糖(Bsp)聚合物可抑制新血管形成并具有三维多孔网络结构,其作为微米结构的第一级(微球),将在肿瘤栓塞和抑制缺血诱导的新血管形成中发挥作用。由Bsp聚合物微球包埋的纳米柔性脂质体作为第二级纳米结构,用于跨生物膜屏障递送药物。通过乳液交联法可轻松形成MN-Ms的微纳二元递进结构。MN-Ms呈完美圆形,具有所需的溶胀和悬浮特性,这对于TCE栓塞操作非常方便。由于二元递进结构,MN-Ms可通过增强二甲基斑蝥酸钠(SC)跨血管壁和组织基质的通透性并延迟给药部位的药物释放,有效地将药物靶向递送至目标肝组织,这使得给药的SC大部分积聚在肝脏中,对人肝癌细胞也具有更高的细胞毒性。这项工作表明,MN-Ms可能是一种用于晚期肝癌TCE应用的有前景的栓塞剂。