EFFECTS OF PLURONIC BLOCK-COPOLYMERS ON DRUG ABSORPTION IN CACO-2 CELL MONOLAYERS

Purpose, The present work characterizes the effects of Pluronic copoly mers on the transport of a P-gp-dependent probe, rhodamine 123 (R123) in Caco-2 cell monolayers. Methods. The accumulation and efflux studie s were performed on the confluent Caco-2 monolayers using fluorescent probes with and without Pluronic copolymers. Results. At concentration s 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 prob e, rhodamine 110 was not altered under these conditions. In contrast t he micelles increased R123 accumulation to a much lower extent when co mpared to the unimers and enhanced R123 efflux in Caco-2 monolayers. C onclusions. Pluronic P85 unimers increase accumulation of a P-gp-depen dent drug in Caco-2 monolayers through inhibition of the P-gp efflux s ystem. The mechanism of the micelle effect is not known, however, it i s very similar to the micelle effects in BBMEC. This has been previous ly shown to involve vesicular transport of the micelle-incorporated dr ug. The study suggests that Pluronic copolymers can be useful in incre asing oral absorption of select drugs.