Effects of pluronic block copolymers on drug absorption in Caco-2 cell monolayers
Effects of pluronic block copolymers on drug absorption in Caco-2 cell monolayers
复制标题
DOI：
10.1023/a:1011964213024
复制
发表时间：
1998-06-01
影响因子：
3.7
通讯作者：
Kabanov, AV
中科院分区：
文献类型：
--
作者：
Batrakova, EV;Han, HY;Kabanov, AV
目的：本研究表征了Pluronic共聚物对p- gp依赖性探针罗丹明123 （R123）在Caco-2细胞单层中运输的影响。用荧光探针对含Pluronic共聚物和不含Pluronic共聚物的Caco-2单层进行了聚积和流出研究。当浓度低于临界胶束浓度时，Pluronic P85单链（“unimers”）增强了R123在Caco-2单层中的积累并抑制了R123的流出。在这些条件下，p- gp无关探针罗丹明110的转运没有改变。与单体相比，胶束增加R123积累的程度要小得多，而在Caco-2单层中，胶束增加了R123的外排。Pluronic P85分子通过抑制P-gp外排系统增加了P-gp依赖药物在Caco-2单层中的积累。胶束效应的机制尚不清楚，但它与BBMEC中的胶束效应非常相似。这先前已被证明涉及胶束结合药物的囊泡运输。该研究表明Pluronic共聚物可用于增加某些药物的口服吸收。
Purpose, The present work characterizes the effects of Pluronic copolymers on the transport of a P-gp-dependent probe, rhodamine 123 (R123) in Caco-2 cell monolayers.Methods. The accumulation and efflux studies were performed on the confluent Caco-2 monolayers using fluorescent probes with and without Pluronic copolymers.Results. At concentrations below the critical micelle concentration single chains ("unimers") of Pluronic P85 enhanced the accumulation and inhibited the efflux of R123 in Caco-2 monolayers. The transport of the P-gp-independent probe, rhodamine 110 was not altered under these conditions. In contrast the micelles increased R123 accumulation to a much lower extent when compared to the unimers and enhanced R123 efflux in Caco-2 monolayers.Conclusions. Pluronic P85 unimers increase accumulation of a P-gp-dependent drug in Caco-2 monolayers through inhibition of the P-gp efflux system. The mechanism of the micelle effect is not known, however, it is very similar to the micelle effects in BBMEC. This has been previously shown to involve vesicular transport of the micelle-incorporated drug. The study suggests that Pluronic copolymers can be useful in increasing oral absorption of select drugs.