Effects of Pluronic P85 unimers and micelles on drug permeability in polarized BBMEC and Caco-2 cells

• Published in: Pharmaceutical research Vol. 15; no. 10; pp. 1525 - 1532
• Main Authors: BATRAKOVA, E. V, HAN, H.-Y, MILLER, D. W, KABANOV, A. V
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.10.1998; Springer Nature B.V
• Subjects: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology; Biological and medical sciences; Biological Transport - drug effects; Blood-Brain Barrier - drug effects; Caco-2 Cells; Cattle; Cell physiology; Cell Polarity; Endothelium, Vascular - metabolism; Fundamental and applied biological sciences. Psychology; General pharmacology; Humans; Intestinal Mucosa - metabolism; Medical sciences; Membrane and intracellular transports; Micelles; Molecular and cellular biology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyethylenes - pharmacology; Polypropylenes - pharmacology; Rhodamine 123 - pharmacokinetics; Human; Rhodamine; Endothelial cell; Pharmaceutical technology; Digestive system; Gut; Micelle; Drug carrier; Permeability; Surfactant; Blood brain barrier; In vitro; Absorption; Membrane transport; Ethylene copolymer; Dosage form; Propylene oxide copolymer; Tumor cell; Block copolymer
• DOI: 10.1023/A:1011942814300
• ISSN: 0724-8741

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