Optimal Structure Requirements for Pluronic Block Copolymers in Modifying P-glycoprotein Drug Efflux Transporter Activity in Bovine Brain Microvessel Endothelial Cells

Pluronic block copolymer P85 was shown to inhibit the P-glycoprotein (Pgp) drug efflux system and to increase the permeability of a broad spectrum of drugs in the blood-brain barrier (BBB). However, there is an entire series of Pluronics varying in lengths of propylene oxide and ethylene oxide and o...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 2003-02, Vol.304 (2), p.845-854
Main Authors: Batrakova, Elena V, Li, Shu, Alakhov, Valery Yu, Miller, Donald W, Kabanov, Alexander V
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - metabolism
Animals
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Biological Transport
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - physiology
Brain - drug effects
Brain - metabolism
Cattle
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Humans
Poloxalene - chemistry
Poloxalene - pharmacology
Structure-Activity Relationship
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Summary:Pluronic block copolymer P85 was shown to inhibit the P-glycoprotein (Pgp) drug efflux system and to increase the permeability of a broad spectrum of drugs in the blood-brain barrier (BBB). However, there is an entire series of Pluronics varying in lengths of propylene oxide and ethylene oxide and overall lipophilicity. This study identifies those structural characteristics of Pluronics required for maximal impact on drug efflux transporter activity in bovine brain microvessel endothelial cells (BBMECs). Using a wide range of block copolymers, differing in hydrophilic-lipophilic balance (HLB), this study shows that lipophilic Pluronics with intermediate length of propylene oxide block (from 30 to 60 units) and HLB
ISSN:0022-3565
1521-0103
DOI:10.1124/jpet.102.043307