Overcoming the Blood Brain Barrier—The Challenge of Brain Drug Targeting

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Abstract:

Drug delivery to the central nervous system (CNS) still remains one of the big challenges in modern medicine. The brain is protected by a capillary network, the so called blood-brain barrier (BBB), which provides a defined neuronal homeostatic environment but restricts access of most pharmaceuticals to the CNS. This limited BBB permeability is partly due to the expression of very tight junctions between endothelial cells as well as due to the presence of export pumps, like p-glycoprotein, and other efflux proteins, which recognize an abundant spectrum of substrates including many CNS drugs. To enhance drug targeting to the CNS and to overcome the BBB several non-invasive approaches derived from medicinal chemistry, pharmacology/physiology and pharmaceutical technology are summarised in the present review: e.g., the direct blockade of export proteins, the chemical modification of CNS drugs to either increase lipophilicity or to achieve selective brain trapping as well as the use of colloidal carriers directed to the BBB. Nanotechnology has revolutionised drug delivery, allowing therapeutic agents to be selectively transferred across the BBB and thus, minimising accumulation in other organs. Here, we focus on vesicular and vector-mediated transport systems. Different types of colloidal drug delivery systems like polymeric nanoparticles, liposomes, solid lipid nanoparticles, polymeric micelles or the use of ultrasound are discussed as well as functionalization of nanocarriers to exploit endogenous BBB transport features. Novel developments on conjugation strategies used to attach biomolecules to the surface of nanocarriers are reviewed as well as their applicability to shuttle drugs across the BBB. Limitations and advantages of each technology are evaluated presenting nano-scaled carriers as potential developing vectors to customize and improve brain drug targeting.

Keywords: BLOOD BRAIN BARRIER; CNS-DRUG DELIVERY; LIPOSOMES; NANOPARTICLES; P-GLYCOPROTEIN

Document Type: Review Article

DOI: http://dx.doi.org/10.1166/jns.2012.1012

Publication date: April 1, 2012

More about this publication?
  • Recent advances in nanomaterials indicates that the central nervous system (CNS) is susceptible to nanoparticle induced alterations leading to functional or structural alterations. This knowledge is currently disseminated in vast array of journals dealing with broad subject areas related to pharmacology, toxicology, neuroscience or nanosciences. Thus, there is an urgent need to collect all these diverse information related to nanoscience and brain function in one place using Journal of Nanoneuroscience for the benefit of the scientific community, researchers, health planners, health care providers, policy makers, environmentalists, biologists, chemists, and physicist in this emerging area of medical science.
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