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.
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.
Authors: A V Kabanov; V P Chekhonin; E V Batrakova; A S Lebedev; N S Melik-Nubarov; S A Arzhakov; A V Levashov; G V Morozov; E S Severin Journal: FEBS Lett Date: 1989-12-04 Impact factor: 4.124
Authors: T J Lampidis; C Castello; A del Giglio; B C Pressman; P Viallet; K W Trevorrow; G K Valet; H Tapiero; N Savaraj Journal: Biochem Pharmacol Date: 1989-12-01 Impact factor: 5.858
Authors: Xiaobin Zhang; Daria Y Alakhova; Elena V Batrakova; Shu Li; Zhihui Yang; Yili Li; Alexander V Kabanov Journal: J Neuroimmune Pharmacol Date: 2008-08-02 Impact factor: 4.147