Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN 47907, United States.
Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN 47907, United States.
J Control Release. 2017 Dec 10;267:214-222. doi: 10.1016/j.jconrel.2017.08.031. Epub 2017 Aug 24.
Formulating a poorly water-soluble drug substance into nanocrystals offers many advantages. Understanding of the in vivo fate of drug nanocrystals is however very limited. In this study, we utilized the hybrid nanocrystal concept and studied the kinetic process of dissolution in cancer cells. By taking advantage of aggregation-induced emission (AIE), hybrid paclitaxel (PTX) nanocrystals integrated with tetraphenylethene (TPE) enabled a novel way for estimating the intracellular dissolution process of the nanocrystals. When TPE is entrapped in a nanocrystal, fluorescence is emitted when the nanocrystal is optically excited. When an entrapped TPE molecule is released to a liquid medium due to the dissolution of the nanocrystal, its fluorescence is quenched. By monitoring the change in fluorescence, it is possible to quantify the dissolution of nanocrystals in a biological environment. Cellular uptake studies of hybrid nanocrystals were conducted with KB and HT-29 cell lines and characterized by confocal microscopy, flow cytometry, and HPLC. The results suggest that drug nanocrystals were taken up directly by the cells, and subsequently dissolved in the cytoplasm. The extent to which the drug nanocrystal dissolved was estimated according to the fluorescence measurement. The cellular uptake and intracellular dissolution could be influenced by drug concentration, incubation time, and surface coating, as well as the type of cell line.
将难溶性药物制成纳米晶体有很多优势。然而，人们对药物纳米晶体的体内命运知之甚少。在本研究中，我们利用杂化纳米晶体的概念研究了纳米晶体在癌细胞中的溶解动力学过程。通过利用聚集诱导发光（AIE），与四苯乙烯（TPE）集成的紫杉醇（PTX）杂化纳米晶体为估计纳米晶体的细胞内溶解过程提供了一种新方法。当 TPE 被包埋在纳米晶体中时，当纳米晶体被光学激发时会发出荧光。当由于纳米晶体的溶解而将包埋的 TPE 分子释放到液体介质中时，其荧光被猝灭。通过监测荧光的变化，可以定量测量纳米晶体在生物环境中的溶解情况。使用 KB 和 HT-29 细胞系进行了杂化纳米晶体的细胞摄取研究，并通过共聚焦显微镜、流式细胞术和 HPLC 进行了表征。结果表明，药物纳米晶体被细胞直接摄取，随后在细胞质中溶解。根据荧光测量估计药物纳米晶体溶解的程度。药物浓度、孵育时间和表面涂层以及细胞系的类型都会影响纳米晶体的细胞摄取和细胞内溶解。
