Pluronic ® block copolymers as modulators of drug efflux transporter activity in the blood–brain barrier

• Published in: Advanced drug delivery reviews Vol. 55; no. 1; pp. 151 - 164
• Main Authors: Kabanov, Alexander V., Batrakova, Elena V., Miller, Donald W.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 21-01-2003
• Subjects: Animals; ATP-Binding Cassette Transporters - antagonists & inhibitors; ATP-Binding Cassette Transporters - metabolism; ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Biological Transport, Active; Block copolymer; Blood-Brain Barrier - drug effects; Blood–brain barrier; Brain - blood supply; Drug Carriers; Drug-Related Side Effects and Adverse Reactions; Endothelium, Vascular - metabolism; Humans; Membrane Transport Modulators; Membrane Transport Proteins - antagonists & inhibitors; Membrane Transport Proteins - metabolism; Multidrug resistance (MDR); Multidrug resistant protein (MRP); P-glycoprotein; Pharmaceutical Preparations - metabolism; Poloxamer - pharmacology; Poloxamer - toxicity; P-glycoprotein; Multidrug resistance (MDR); Multidrug resistant protein (MRP); Block copolymer; Blood–brain barrier
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/S0169-409X(02)00176-X

Drug efflux transporters can influence the absorption, tissue distribution and elimination of many therapeutic agents. Modulation of drug efflux transporter activity is being explored as a means for improving the pharmacokinetic and pharmacodynamic properties of various drugs. In this regard, several polymer formulations have been shown to inhibit drug efflux transporters such as P-glycoprotein (P-gp). The current review will focus on Pluronic
® block copolymers in particular, the mechanisms involved in the effects of Pluronic
® on drug efflux transporters, and the optimal polymer compositions required for inhibition of drug efflux transporters. Special emphasis will be placed on the potential applications of Pluronic
® in enhancing the blood–brain barrier (BBB) penetration of drugs.