Effects of stability of PEGylated micelles on the accelerated blood clearance phenomenon
Effects of stability of PEGylated micelles on the accelerated blood clearance phenomenon
复制标题
DOI：
10.1007/s13346-018-0588-3
复制
发表时间：
2018-10
影响因子：
5.4
通讯作者：
Yuqing Su;Mengyang Liu;Yan Xiong;Junqiang Ding;Xinrong Liu;Yanzhi Song;Yihui Deng
中科院分区：
文献类型：
--
作者：
Yuqing Su;Mengyang Liu;Yan Xiong;Junqiang Ding;Xinrong Liu;Yanzhi Song;Yihui Deng
加速血液清除（ABC）是载体系统的血液清除率显著提高的现象。它可以通过重复注射聚乙二醇（PEG）（分子量2000）改性胶束（PM 2000）诱导。为了确定PEG链长和PEG化胶束注射剂量是否对ABC现象有影响，用不同分子量的PEG修饰胶束;使用分子量为350、550、2000、5000、10，000和20，000的PEG来产生PEG化胶束PM 350、PM 550、PM 2000、PM 10,000、PM 2000和PM 20,000。和PM20000。一种特殊的载体MCT-PM 2000是用原始PM 2000制剂制备的，但也包含额外的中链甘油三酯。我们的实验结果表明，与PM 350、PM 550、PM 10000和PM 20000相比，PM 2000和PM 5000表现出上级的储存稳定性。MCT-PM 2000显示出比PM 2000更强的稀释稳定性。正如预期，与PM 350、PM 550、PM 10000和PM 20000相比，PM 2000和PM 5000诱导的血液消除速率增强最强;与PM 2000相比，MCT-PM 2000显示出更强烈的ABC现象。此外，当注射剂量从0.05 μmol磷脂·kg− 1增加至5 μmol磷脂·kg−1时，PM 2000和MCT-PM 2000对ABC现象的诱导增强。基于我们的研究结果，我们认为，有一个积极的线性关系之间的稳定性PEG修饰的胶束和敏感性的ABC现象。这一结果对设计用于多种药物治疗的聚乙二醇化胶束具有一定的参考价值。
Accelerated blood clearance (ABC) is a phenomenon where the blood clearance rate of the carrier system is substantially raised. It can be induced by repetitive injections of polyethylene glycol (PEG) (molecular weight 2000)-modified micelles (PM2000). To determine whether the PEG chain length and PEGylated micelle injection dose can have an effect on the ABC phenomenon, micelles were modified with PEGs of varying molecular weights; PEGs with molecular weights of 350, 550, 2000, 5000, 10,000, and 20,000 were used to generate the PEGylated micelles PM350, PM550, PM2000, PM10000, and PM20000, respectively. One special carrier, MCT-PM2000, was prepared with the original PM2000 formulation but also included extra medium-chain triglycerides. Our experimental results showed that PM2000 and PM5000 exhibit superior storage stability compared to that of PM350, PM550, PM10000, and PM20000. MCT-PM2000 demonstrated stronger dilution stability than PM2000. As expected, PM2000 and PM5000 induced the strongest enhancement in blood elimination rate compared to that of PM350, PM550, PM10000, and PM20000; MCT-PM2000 exhibited more intense ABC phenomenon compared to that of PM2000. In addition, induction of the ABC phenomenon by PM2000 and MCT-PM2000 was augmented when the injection dose was increased from 0.05 to 5 μmol phospholipid·kg−1. Based on our findings, we suggest that there is a positive linear relationship between stability of PEG-modified micelles and susceptibility to the ABC phenomenon. The results may be valuable for designing PEGylated micelles for multiple drug therapy.