Investigation of the micellar effect of pluronic P85 on P-glycoprotein inhibition: cell accumulation and equilibrium dialysis studies.
Investigation of the micellar effect of pluronic P85 on P-glycoprotein inhibition: cell accumulation and equilibrium dialysis studies.
复制标题
DOI：
10.1002/jps.21723
复制
发表时间：
2009-11
影响因子：
3.8
通讯作者：
Elmquist, William F.
中科院分区：
文献类型：
--
作者：
Shaik, Naveed;Giri, Nagdeep;Elmquist, William F.
关键词：
The objective of this study was: (1) to characterize the P-gp inhibitory effect of different concentrations of Pluronic P85 on anti-HIV-1drug cellular accumulation, and (2) to investigate the relationship between cellular accumulation and free fraction of drug. Cellular accumulation studies in MDCKII-WT and MDCKII-MDR1 cell monolayers showed a biphasic dose response characterized by decline in accumulation at Pluronic concentrations greater than the CMC. This phenomenon was independent of the inhibition of P-gp efflux by Pluronic. Cell-free equilibrium dialysis was used to determine the effect of Pluronic P85 on drug free fraction and the affinity of Pluronic micelles for drug was modeled. Nelfinavir and saquinavir associated extensively with micelles and equilibrium free fractions were low at P85 concentrations above the CMC, with association constants being in the order nelfinavir > saquinavir >>> abacavir. Abacavir, a P-gp substrate, showed no association with micelles yet showed a biphasic response in cellular accumulation. These data suggest that, above the CMC, inhibition of P-gp is not affected but rather factors such as micellar trapping could contribute to decreased accumulation. Therefore, the in vitro evaluation of the effect of Pluronic formulations on active transport should take into account both the physicochemical properties of drug and the composition of Pluronic.
登录
查看更多内容
影响因子：
3.4
作者：
Bardelmeijer, HA;Ouwehand, M;van Tellingen, O
通讯作者：
van Tellingen, O
影响因子：
3.7
作者：
Ameller, T;Marsaud, R;Renoir, JM
通讯作者：
Renoir, JM
影响因子：
4.9
作者：
Batrakova, Elena V.;Kelly, David L.;Kabanov, Alexander V.
通讯作者：
Kabanov, Alexander V.
影响因子：
6.1
作者：
Alakhov, V Y;Kabanov, A V
通讯作者：
Kabanov, A V
影响因子：
3.7
作者：
Batrakova, EV;Han, HY;Kabanov, AV
通讯作者：
Kabanov, AV