薬物代謝と毒性学ジャーナル
オープンアクセス

概要

Molecular-Mediated Difference Action of Poloxham124/188: Absorption, Efflux and Suborganelle Accumulation in Caco-2 Cells

Xiaoying Lin, Xinxin Zhou, Feng Hao, Lele Li, Yue Cui, Yanfei Zhang, Jiao Guan, Heyun Zhu, Bo Feng

Poloxamers (PLs) are commonly used pharmaceutical excipients. According to the different molecular weight, mainly PL124 and PL188 are observed. PL188 with the larger weight, hydrophilic and more application in oral exposure drug delivery systems than PL124. However, the absorption and transport mechanisms of PL188 into intestinal epithelial cells are still unclear. In this study, we study the uptake and efflux of PL124/188 in Caco-2 cells, and subcellular accumulation in Caco-2 cells quantitatived by ultra-high-performance liquid chromatography-triple/time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). The results showed that, the uptake in Caco-2 cells are different: Both PL188 and 124 entered Caco-2 cells through active transport, but PL188 uptake into Caco-2 cells relies on pinocytosis pathway, fosselin-mediated endocytosis pathway, and the endocytosis pathway independent of mestin and fosselin-mediated endocytosis. While PL124 uptake by independent of clathrin- and fossa-mediated endocytosis inhibitors pathway; The effects of PL188 on P-gp protein substrate were different: PL188 was stronger than PL124; There are also differences in subcellular accumulations: PL124 reaches the cell membrane at a slower rate compared to PL188, which rapidly enters the cytoplasm and nucleus, with a higher concentration in the cytoplasm. Both PL124 and PL188 remain in the skeleton. This work provides data basis for our subsequent application of PL188 and PL124 as oral preparations.