College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Eur J Pharm Sci. 2018 Mar 1;114:210-216. doi: 10.1016/j.ejps.2017.12.010. Epub 2017 Dec 14.
The markers are the "revealers" of accelerated blood clearance (ABC) phenomenon. PEGylated nanocarriers labeled with various markers have been used to explore the mechanism of ABC. However, different markers were labeled on different nanocarriers, and the influence of different markers on ABC phenomenon is questionable. In this study, tocopheryl nicotinate (TN), N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine, triethylammonium salt (NBD-DPPE), and 1,1'-dioctadecyl-3,3,3',3'-tetra-methylindotricarbocyanine iodide (DiR) were selected as markers. ABC index was used as an evaluation indicator to reveal ABC phenomenon after repeated injections of PEGylated emulsions (PEs) in Wistar rats. No significant difference was observed in ABC index of PE labeled with the three markers (P>0.05), suggesting that the results of previous studies using these markers were comparable and interchangeable. Of the three markers, TN required tedious analytical method and showed proliferative effect on liver cells, while NBD-DPPE fluorescence was easily interfered by tissues and its phospholipid composition affected ABC analysis. On the contrary, DiR was deemed superior due to its near-infrared fluorescence, high-sensitivity, and convenient analytical detection.
这些标记物是加速血液清除（ABC）现象的“揭示者”。已将各种标记物标记的聚乙二醇化纳米载体用于探索 ABC 机制。然而，不同的标记物标记在不同的纳米载体上，不同标记物对 ABC 现象的影响值得怀疑。在这项研究中，生育酚烟酸（TN）、N-（7-硝基苯并-2-氧杂-1,3-二唑-4-基）-1,2-二十六烷酰基-sn-甘油-3-磷酸乙醇胺，三乙基铵盐（NBD-DPPE）和 1,1'-二十八基-3,3,3',3'-四甲基吲哚碳菁碘化物（DiR）被选为标记物。ABC 指数被用作评估指标，以揭示 Wistar 大鼠反复注射聚乙二醇化乳剂（PEs）后的 ABC 现象。用这三种标记物标记的 PE 的 ABC 指数没有显著差异（P>0.05），这表明先前使用这些标记物的研究结果是可比和可互换的。在这三种标记物中，TN 需要繁琐的分析方法，并对肝细胞表现出生长作用，而 NBD-DPPE 荧光容易受到组织的干扰，其磷脂组成会影响 ABC 分析。相反，DiR 由于其近红外荧光、高灵敏度和方便的分析检测而被认为更优越。
