New technologies for drug delivery across the blood brain barrier

被引:102
作者
Kabanov, AV [1 ]
Batrakova, EV [1 ]
机构
[1] Univ Nebraska, Med Ctr, Coll Pharm, Dept Pharmaceut Sci,Nebraska Med Ctr 986025, Omaha, NE 68198 USA
关键词
blood-brain barrier; drug efflux; drug delivery; fatty acylation; nanogel; nanoparticles; pluronic block copolymers; poloxamer;
D O I
10.2174/1381612043384826
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The blood-brain barrier (BBB) efficiently restricts penetration of therapeutic agents to the brain from the periphery. Therefore. discovery of new modalities allowing for effective delivery of drugs and biomacromolecules to the central nervous system (CNS) is of great need and importance for treatment of neurodegenerative disorders. This manuscript focuses on three relatively new strategies. The first strategy involves inhibition of the drug efflux transporters expressed in BBB by Pluronic((R)) block copolymers, which allows for the increased transport of the substrates of these transporters to the brain. The second strategy involves the design of nanoparticles conjugated with specific ligands that can target receptors in the brain microvasculature and carry the drugs to the brain through the receptor mediated transcytosis. The third strategy involves artificial hydrophobization of peptides and proteins that facilitates the delivery of these peptides and proteins across BBB. This review discusses the current state, advantages and limitations of each of the three technologies and outlines their future prospects.
引用
收藏
页码:1355 / 1363
页数:9
相关论文
共 102 条
[1]   Transporting therapeutics across the blood-brain barrier [J].
Abbott, NJ ;
Romero, IA .
MOLECULAR MEDICINE TODAY, 1996, 2 (03) :106-113
[2]  
Alakhov V Y, 1998, Expert Opin Investig Drugs, V7, P1453, DOI 10.1517/13543784.7.9.1453
[3]   Hypersensitization of multidrug resistant human ovarian carcinoma cells by pluronic P85 block copolymer [J].
Alakhov, VY ;
Moskaleva, EY ;
Batrakova, EV ;
Kabanov, AV .
BIOCONJUGATE CHEMISTRY, 1996, 7 (02) :209-216
[4]  
ALAKHOV VY, 1990, BIOTECHNOL APPL BIOC, V12, P94
[5]   Liposomes - Opportunities in drug delivery [J].
Allen, TM .
DRUGS, 1997, 54 (Suppl 4) :8-14
[6]   Is obesity a disease of the blood-brain barrier? Physiological, pathological, and evolutionary considerations [J].
Banks, WA .
CURRENT PHARMACEUTICAL DESIGN, 2003, 9 (10) :801-809
[7]   Strategies for the delivery of leptin to the CNS [J].
Banks, WA ;
Lebel, CP .
JOURNAL OF DRUG TARGETING, 2002, 10 (04) :297-308
[8]   Fundamental relationships between the composition of Pluronic block copolymers and their hypersensitization effect in MDR cancer cells [J].
Batrakova, E ;
Lee, S ;
Li, S ;
Venne, A ;
Alakhov, V ;
Kabanov, A .
PHARMACEUTICAL RESEARCH, 1999, 16 (09) :1373-1379
[9]  
Batrakova EV, 2001, J PHARMACOL EXP THER, V299, P483
[10]   Optimal structure requirements for pluronic block copolymers in modifying P-glycoprotein drug efflux transporter activity in bovine brain microvessel endothelial cells [J].
Batrakova, EV ;
Li, S ;
Alakhov, VY ;
Miller, DW ;
Kabanov, AV .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 304 (02) :845-854