School of Pharmacy, Shenyang Pharmaceutical University, 26 Huatuo Road, Benxi, 117004, People's Republic of China.
Drug Deliv Transl Res. 2019 Feb;9(1):66-75. doi: 10.1007/s13346-018-0588-3.
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. 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.
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）修饰的胶束（PM2000）来诱导。为了确定 PEG 链长和 PEG 化胶束注射剂量是否会对 ABC 现象产生影响，我们用不同分子量的 PEG 对胶束进行了修饰；使用分子量为 350、550、2000、5000、10000 和 20000 的 PEG 分别生成 PEG 化胶束 PM350、PM550、PM2000、PM10000 和 PM20000。一种特殊的载体 MCT-PM2000 是用原始的 PM2000 配方制备的，但也包含了额外的中链甘油三酯。我们的实验结果表明，PM2000 和 PM5000 与 PM350、PM550、PM10000 和 PM20000 相比，具有更好的储存稳定性。MCT-PM2000 的稀释稳定性强于 PM2000。正如预期的那样，PM2000 和 PM5000 与 PM350、PM550、PM10000 和 PM20000 相比，诱导血液消除率的增强作用最强；与 PM2000 相比，MCT-PM2000 表现出更强的 ABC 现象。此外，当注射剂量从 0.05 增加到 5μmol 磷脂·kg 时，PM2000 和 MCT-PM2000 诱导的 ABC 现象增强。基于我们的发现，我们认为 PEG 修饰胶束的稳定性与对 ABC 现象的易感性之间存在正线性关系。这些结果可能对设计用于多种药物治疗的 PEG 化胶束具有重要意义。
