Su Yuqing, Wang Lirong, Liang Kaifan, Liu Mengyang, Liu Xinrong, Song Yanzhi, Deng Yihui
Shenyang Pharmaceutical University, No.85, Hongliu Road, Benxi 117004, China.
Asian J Pharm Sci. 2018 Jan;13(1):44-53. doi: 10.1016/j.ajps.2017.07.003. Epub 2017 Aug 7.
For investigating the accelerated blood clearance (ABC) phenomenon of polyglycerin modified nanoemulsions upon cross administration with polyethylene glycol (PEG) covered nanoemulsion, we used the 1,2-distea-royl-sn-glycero-3-phosphoethanolamine-n-polyglycerine-610 and the 1,2-distearoyl-n-glycero-3-phosphoethanolamine-n-[me-thoxy(polyethylene glycol)-2000] as modify materials, the dialkylcarbocyanines as fluorescence indicator. Exhausted macrophages rat model was established and new material containing polycarboxyl structure was synthesized. The microplate reader and the optical imaging system were applied to measure the concentration of nanoemulsions in tissues. The results show that the first dose of polyglycerin modified nanoemulsion can induce the ABC phenomenon of the second dose of PEGylated nanoemulsion. With the increase in the amount of the surface polyglycerin, the extent of the ABC phenomenon decreases. Liver accumulation has positive relationship with the ABC phenomenon. Furthermore, kupffer cells in liver can get more immune information from polyhydroxy structure than polycarboxyl group in the modify compound. The results of our work imply that the polycarboxyl structure has advantages to eliminate the ABC phenomenon.
为研究聚甘油修饰的纳米乳剂与聚乙二醇（PEG）包覆的纳米乳剂交叉给药时的加速血液清除（ABC）现象，我们使用1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-n-聚甘油-610和1,2-二硬脂酰-n-甘油-3-磷酸乙醇胺-n-[甲氧基（聚乙二醇）-2000]作为修饰材料，二烷基碳菁作为荧光指示剂。建立了巨噬细胞耗竭大鼠模型并合成了含多羧基结构的新材料。应用酶标仪和光学成像系统测量纳米乳剂在组织中的浓度。结果表明，第一剂聚甘油修饰的纳米乳剂可诱导第二剂聚乙二醇化纳米乳剂的ABC现象。随着表面聚甘油量的增加，ABC现象的程度降低。肝脏蓄积与ABC现象呈正相关。此外，肝脏中的库普弗细胞从修饰化合物中的多羟基结构比多羧基基团能获得更多的免疫信息。我们的工作结果表明，多羧基结构在消除ABC现象方面具有优势。
