Pluronic block copolymers: Evolution of drug delivery concept from inert nanocarriers to biological response modifiers

被引:1038
作者
Batrakova, Elena V. [1 ]
Kabanov, Alexander V. [2 ]
机构
[1] Univ Nebraska, Med Ctr, Coll Pharm, Dept Pharmaceut Sci,Ctr Drug Delivery & Nanomed, Omaha, NE 68198 USA
[2] Moscow MV Lomonosov State Univ, Dept Chem, Moscow, Russia
基金
美国国家卫生研究院;
关键词
pluronic; nanocarrier; multidrug resistance; biological response modifiers; drug delivery system;
D O I
10.1016/j.jconrel.2008.04.013
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Polymer nanomaterials have sparked a considerable interest as vehicles used for diagnostic and therapeutic agents; research in nanomedicine has not only become a frontier movement but is also a revolutionizing drug delivery Held. A common approach for building a drug delivery system is to incorporate the drug within the nanocarrier that results in increased solubility, metabolic stability, and improved circulation time. With this foundation, nanoparticles with stealth properties that can circumvent RES and other clearance and defense mechanisms are the most promising. However, recent developments indicate that select polymer nanomaterials can implement more than only inert carrier functions by being biological response modifiers. One representative of such materials is Pluronic block copolymers that cause various functional alterations in cells. The key attribute for the biological activity of Pluronics is their ability to incorporate into membranes followed by Subsequent translocation into the cells and affecting various cellular functions, such as mitochondrial respiration, ATP synthesis, activity of drug efflux transporters, apoptotic signal transduction, and gene expression. As a result. Pluronics cause drastic sensitization of MDR tumors to various anticancer agents, enhance drug transport across the blood brain and intestinal barriers, and causes transcriptional activation of gene expression both in vitro and in vivo. Collectively, these studies suggest that Pluronics have a broad spectrum of biological response modifying activities which make it one of the most potent drug targeting systems available, resulting in a remarkable impact on the emergent held of nanomedicine. Published by Elsevier B.V.
引用
收藏
页码:98 / 106
页数:9
相关论文
共 90 条
[1]   Block copolymeric biotransport carriers as versatile vehicles for drug delivery [J].
Alakhov, V ;
Klinski, E ;
Lemieux, P ;
Pietrzynski, G ;
Kabanov, A .
EXPERT OPINION ON BIOLOGICAL THERAPY, 2001, 1 (04) :583-602
[2]   Block copolymer-based formulation of doxorubicin. From cell screen to clinical trials [J].
Alakhov, V ;
Klinski, E ;
Li, SM ;
Pietrzynski, G ;
Venne, A ;
Batrakova, E ;
Bronitch, T ;
Kabanov, A .
COLLOIDS AND SURFACES B-BIOINTERFACES, 1999, 16 (1-4) :113-134
[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]  
BAE KH, 2008, BIOMATERIALS
[5]   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
[6]   Alteration of genomic responses to doxorubicin and prevention of MDR in breast cancer cells by a polymer excipient: Pluronic P85 [J].
Batrakova, Elena V. ;
Kelly, David L. ;
Li, Shu ;
Li, Yili ;
Yang, Zhihui ;
Xiao, Li ;
Alakhova, Daria Y. ;
Sherman, Simon ;
Alakhov, Valery Yu. ;
Kabanov, Alexander V. .
MOLECULAR PHARMACEUTICS, 2006, 3 (02) :113-123
[7]   Effect of pluronic p85 on ATPase activity of drug efflux transporters [J].
Batrakova, EV ;
Li, S ;
Li, YL ;
Alakhov, VY ;
Kabanov, AV .
PHARMACEUTICAL RESEARCH, 2004, 21 (12) :2226-2233
[8]   Distribution kinetics of a micelle-forming block copolymer Pluronic P85 [J].
Batrakova, EV ;
Li, S ;
Li, YL ;
Alakhov, VY ;
Elmquist, WF ;
Kabanov, AV .
JOURNAL OF CONTROLLED RELEASE, 2004, 100 (03) :389-397
[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