Targeted Drug Delivery Across Blood-Brain-Barrier Using Cell Penetrating Peptides Tagged Nanoparticles

被引:32
作者
Malhotra, Meenakshi
Prakash, Satya [1 ,2 ]
机构
[1] McGill Univ, Fac Med, Artificial Cells & Organs Res Ctr, Biomed Technol & Cell Therapy Res Lab,Dept Biomed, Montreal, PQ H3A 2B4, Canada
[2] McGill Univ, Fac Med, Artificial Cells & Organs Res Ctr, Biomed Technol & Cell Therapy Res Lab,Dept Physio, Montreal, PQ H3A 2B4, Canada
关键词
Polymeric nanoparticles; blood-brain barrier; cell penetrating peptides; multifunctionality; targeted delivery; nanocapsules; nanomedicine; nanotechnology; CENTRAL-NERVOUS-SYSTEM; VIVO PROTEIN TRANSDUCTION; ARGININE-RICH PEPTIDES; IN-VITRO MODEL; INTRACELLULAR DELIVERY; MEDIATED TRANSPORT; PARKINSONS-DISEASE; BLOCK-COPOLYMERS; P-GLYCOPROTEIN; GROWTH-FACTOR;
D O I
10.2174/157341311794480336
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
In the field of biomedical sciences, nanotechnology has emerged as a novel approach to design and develop drug delivery carriers (i.e. nanoparticles). The inspiration of nanoparticles as delivery vehicles for drugs or genes arose from the concept of viral mediated delivery. Researchers envied the enhanced transport efficiency of viruses but required a delivery method that did not incorporate the virus-induced pathological, immunological and oncological side-effects. Thus, bio-mimicked nanoparticles were prepared from synthetic polymers for efficient delivery of therapeutic molecules. However, biotherapeutics delivery across blood-brain-barrier is still a challenging task due to the inherent neuroprotective mechanism of the human brain. Recent studies suggest that cationic cell penetrating peptides can be used in designing targeted nanoparticles. This review describes the anatomical and physiological barriers of the brain with their special features and limitations for drug delivery and role of cationic cell penetrating peptides in designing nanoparticles for targeted biotherapeutics delivery to the brain. It emphasises the use of polymeric nanoparticles and their characteristics with respect to size, surface tolerability and multifunctionality. These properties aid them to cross the biological barriers of the brain. The multifunctionality of nanoparticles has been further explored with the application of cell penetrating peptides conjugated with nanoparticles for delivery at specialized location. The utilization of peptides on nanoparticles has encouraged and facilitated the approach of using non-invasive techniques not only to deliver drugs but also genes and proteins with minimal side-effects and toxicity when compared to conventional invasive techniques of therapeutic delivery to the brain. This technology has shown to be promising as a possible treatment method for a number of neurological disorders in both in vitro and in vivo models.
引用
收藏
页码:81 / 93
页数:13
相关论文
共 208 条
[61]   Blood-brain interfaces: Relevance to cerebral drug metabolism [J].
GhersiEgea, JF ;
LeiningerMuller, B ;
Cecchelli, R ;
Fenstermacher, JD .
TOXICOLOGY LETTERS, 1995, 82-3 :645-653
[62]   Influence of preparation conditions on acyclovir-loaded poly-d,l-lactic acid nanospheres and effect of PEG coating on ocular drug bioavailability [J].
Giannavola, C ;
Bucolo, C ;
Maltese, A ;
Paolino, D ;
Vandelli, MA ;
Puglisi, G ;
Lee, VHL ;
Fresta, M .
PHARMACEUTICAL RESEARCH, 2003, 20 (04) :584-590
[63]   Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles [J].
Gulyaev, AE ;
Gelperina, SE ;
Skidan, IN ;
Antropov, AS ;
Kivman, GY ;
Kreuter, J .
PHARMACEUTICAL RESEARCH, 1999, 16 (10) :1564-1569
[64]   The blood-brain barrier/neurovascular unit in health and disease [J].
Hawkins, BT ;
Davis, TP .
PHARMACOLOGICAL REVIEWS, 2005, 57 (02) :173-185
[65]   Striatal delivery of CERE-120, an AAV2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys [J].
Herzog, Christopher D. ;
Dass, Biplob ;
Holden, James E. ;
Stansell, James, III ;
Gasmi, Mehdi ;
Tuszynski, Mark H. ;
Bartus, Raymond T. ;
Kordower, Jeffrey H. .
MOVEMENT DISORDERS, 2007, 22 (08) :1124-1132
[66]   Preparation and purification of cationic solid lipid nanospheres - effects on particle size, physical stability and cell toxicity [J].
Heydenreich, AV ;
Westmeier, R ;
Pedersen, N ;
Poulsen, HS ;
Kristensen, HG .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2003, 254 (01) :83-87
[67]   Lactoferrin-conjugated PEG-PLA nanoparticles with improved brain delivery: In vitro and in vivo evaluations [J].
Hu, Kaili ;
Li, Jingwei ;
Shen, Yehong ;
Lu, Wei ;
Gao, Xiaoling ;
Zhang, Qizhi ;
Jiang, Xinguo .
JOURNAL OF CONTROLLED RELEASE, 2009, 134 (01) :55-61
[68]   Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier [J].
Huber, JD ;
Egleton, RD ;
Davis, TP .
TRENDS IN NEUROSCIENCES, 2001, 24 (12) :719-725
[69]   Brain-specific expression of vascular endothelial growth factor 146 correlates with the blood-brain barrier induction in quail embryos [J].
Ikeda, Eiji ;
Takubo, Keiyo ;
Kodama, Takahide ;
Okada, Yasunori .
DEVELOPMENTAL NEUROSCIENCE, 2008, 30 (05) :331-339
[70]   Nasal drug delivery: new developments and strategies [J].
Illum, L .
DRUG DISCOVERY TODAY, 2002, 7 (23) :1184-1189