Pluronic block copolymers as modulators of drug efflux transporter activity in the blood-brain barrier.
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.
Kabanov
Alexander V
AV
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198, USA. akabanov@unmc.edu
Batrakova
Elena V
EV
Miller
Donald W
DW
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply; D004337:Drug Carriers; D064420:Drug-Related Side Effects and Adverse Reactions; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D020442:Poloxamer / Q000494:pharmacology* / Q000633:toxicity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D004337:Drug Carriers; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; D004364:Pharmaceutical Preparations; D020442:Poloxamer