{"id":5703,"date":"2014-05-16T09:49:26","date_gmt":"2014-05-16T07:49:26","guid":{"rendered":"https:\/\/dana.ggiants.de\/nanoparticles-at-the-blood-brain-barrier\/"},"modified":"2024-11-05T15:16:34","modified_gmt":"2024-11-05T14:16:34","slug":"nanoparticles-at-the-blood-brain-barrier","status":"publish","type":"page","link":"https:\/\/materialneutral.info\/en\/safety\/body-barriers\/nanoparticles-at-the-blood-brain-barrier\/","title":{"rendered":"Nanoparticles at the Blood-Brain Barrier"},"content":{"rendered":"

The blood-brain barrier separates the vascular system from the brain and is formed by endothelial cells<\/span> which are enclosing the brain capillary blood vessels. Under normal circumstances this barrier is impermeable to nanoparticles.<\/p>\n

The cellular barrier, which separates the brain from the vascular system, is formed by endothelial cells [1]<\/sup>. Our capillary blood vessels are enclosed with these cells (endothelial cells), that are connected to each other with circumventing tight junctions<\/span> that abolish all substance transport between the cells. Only very small lipophilic<\/span> molecules can overcome this cellular barrier by passive diffusion<\/span>. In addition, these cells possess very effective efflux carriers that transport most of these lipophilic substances directly back into the blood stream. Taken together these mechanisms ensure a fully functioning barrier against most substances [2,3]<\/sup>.<\/p>\n

\"Schematic
Schematic sketch showing the blood-brain barrier. From the brain down to the tight junctions. © von Kuebi = Armin Kübelbeck, and for the brain: Patrick J. Lynch [CC-BY-3.0 (http:\/\/creativecommons.org\/licenses\/by\/3.0)], via Wikimedia Commons<\/figcaption><\/figure>\n

If particulates such as nanoparticles or liposomes<\/span> are to overcome this cellular barrier they need to be equipped with a specifically adapted surface modification<\/span>. This principle applies to both inorganic (e.g. Gold<\/a>, Iron<\/a>) and organic nanoparticles (e.g. lipid-, peptide<\/span> or protein-based) [4,5]<\/sup>.<\/p>\n

In order to ensure the supply of the brain with essential nutrients and also to enable the interaction with the residual body, endothelial cells have specific receptors on the outside that actively transport the binding partners into the brain using the lock-and-key principle [3]<\/sup>. Nutrients such as amino acids, glucose and also important messenger or metabolic substances (proteins, hormones) are reckoned as such possible binding partners [3]<\/sup>.<\/p>\n

This carrier-system can also be used to enable the transport of nanoparticles into the brain. For this purpose, respective ligands that fit like a key into the lock of these transporters have to be linked directly (with a covalent bound) or indirectly (by adsorption<\/span> processes) to the surface of the particles. Such modified nanoparticles can now act as “Trojan horses”<\/em>[6]<\/sup>. These modifications can only be achieved by usage of selective chemical or physico-chemical processes as in nature such linking procedures do not take place. For this reason in general nanoparticles do not cross the blood-brain barrier.<\/p>\n

This method offers great opportunities for medical applications as it is now possible to attach a number of drugs and other biologically active materials to the nanoparticles like doxorubicin<\/a>, which is used in chemotherapy against brain tumours [7,8]<\/sup> or other drugs for the treatment of neurodegenerative diseases [9,10]<\/sup>. In case of cancer treatment, these drugs are administered intravenously<\/span>, are then transported through the blood and via the blood-brain barrier into the brain where they
\nreach the tumour, their final destination. Without these coatings and attached binding partners the same nanoparticles would be ineffective. The ligands currently used include various proteins [5,11-13]<\/sup> as well as specific antibodies<\/a>[12,13]<\/sup>.<\/p>\n

Good biocompatibility<\/span> and rapid biodegradation of the nanoparticle<\/span> carrier materials are the prerequisites for the use of such coated<\/span> nanoparticles in medical applications [6]<\/sup>. Therefore, from today’s perspective only specifically prepared organic carrier materials are suitable for this purpose.<\/p>\n

Since these ligands can equally be attached to inorganic materials it is also possible to transport e.g. gold nanoparticles into the brain using this mechanism [14]<\/sup>. However, these particles lack rapid biodegradation and thus do not fulfil the mentioned requirements making them unsuitable for usage in humans. Iron nanoparticles that are employed for diagnostic purposes can also be transported across the blood-brain barrier after their incorporation into solid lipid nanoparticles (SLN)<\/a> combined with a special coating [15,16]<\/sup>. However, up-to-now the necessary toxicological and elimination studies for an application in humans are missing. Carbon nanotubes<\/a> (CNTs) are not suitable as drug carriers for brain applications due to their needle-like shape and lacking biodegradability [17]<\/sup>.<\/p>\n


Literature<\/em><\/strong><\/span><\/p>\n

    \n
  1. Reese, TS et al. (1967). J Cell Biol, 34(1): 207-217.<\/a><\/span><\/li>\n
  2. Begley, DJ (2004). Pharmacol Ther, 104(1): 29-45.<\/a><\/span><\/li>\n
  3. Abbott, NJ et al. (2010). Neurobiol Dis, 37(1): 13-25.<\/a><\/span><\/li>\n
  4. Fabian, E et al. (2008). Arch Toxicol, 82(3): 151-157.<\/a><\/span><\/li>\n
  5. Zensi, A et al. (2009). J Control Release, 137(1): 78-86.<\/a><\/span><\/li>\n
  6. Wohlfart, S et al. (2012). J Control Release, 161(2): 264-273.<\/a><\/span><\/li>\n
  7. Gulyaev, AE et al. (1999). Pharm Res 16, 1564–1569<\/a><\/span><\/li>\n
  8. Steiniger, SC et al. (2004). Int J Cancer, 109(5): 759-767.<\/a><\/span><\/li>\n
  9. Kreuter, J et al. (1995). Brain Res, 674(1): 171-174.<\/a><\/span><\/li>\n
  10. Kurakhmaeva, KB et al. (2009). J Drug Target, 17(8): 564-574.<\/a><\/span><\/li>\n
  11. Kreuter, J et al. (2007). J Control Release, 118(1): 54-58.<\/a><\/span><\/li>\n
  12. Ulbrich, K et al. (2009). Eur J Pharm Biopharm, 71(2): 251-256.<\/a><\/span><\/li>\n
  13. Ulbrich, K et al. (2011). J Drug Target, 19(2): 125-132.<\/a><\/span><\/li>\n
  14. Wiley, DT et al. (2013). PNAS, 110(21): 8662-8667.<\/a><\/span><\/li>\n
  15. Zara, GP et al. (2002). J Drug Target, 10(4): 327-335.<\/a><\/span><\/li>\n
  16. Peira, E et al. (2003). J Drug Target, 11(1): 19-24.<\/a><\/span><\/li>\n
  17. Yang, ST et al. (2007). J Phys Chem C 111(48): 17761-17764.<\/a><\/span><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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