Effects of pluronic P85 unimers and micelles on drug permeability in polarized BBMEC and Caco-2 cells.
OBJECTIVE
Using polarized bovine brain microvessel endothelial cells (BBMEC) monolayers as in vitro model of the blood brain barrier and Caco-2 monolayers as a model of the intestinal epithelium, the present work investigates the effects of Pluronic P85 block copolymer (P85) on the transport of the P-gycoprotein (P-gp)- dependent probe, rhodamine 123 (R123).


METHODS
The permeability and cell efflux studies are performed with the confluent cell monolayers using Side-Bi-Side diffusion cells.


RESULTS
At concentrations below the critical micelle concentration, P85 inhibits P-gp efflux systems of the BBMEC and Caco-2 cell monolayers resulting in an increase in the apical to basolateral permeability of R123. In contrast, at high concentrations of P85 the drug incorporates into the micelles, enters the cells and is then recycled back out to the apical side resulting in decrease in R123 transport across the cell monolayers. Apical to basolateral permeability of micelle-incorporated R123 in BBMEC monolayers was increased by prior conjugation of P85 with insulin, suggesting that modified micelles undergo receptor-mediated transcytosis.


CONCLUSIONS
Pluronic block copolymers can increase membrane transport and transcellular permeability in brain microvessel endothelial cells and intestinal epithelium cells. This suggests that these block copolymers may be useful in designing formulations to increase brain and oral absorption of select drugs.
Batrakova
E V
EV
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha 68198, USA.
Han
H Y
HY
Miller
D W
DW
Kabanov
A V
AV
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects*; D018938:Caco-2 Cells; D002417:Cattle; D016764:Cell Polarity; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008823:Micelles; D011095:Polyethylenes / Q000494:pharmacology*; D011126:Polypropylenes / Q000494:pharmacology*; D020112:Rhodamine 123 / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008823:Micelles; D011095:Polyethylenes; D011126:Polypropylenes; D020112:Rhodamine 123