After intraveneous injection, nanoparticles are taken up very rapidly by the reticuloendothelial system (RES) and distribute especially into the liver (60-90%) and spleen (2-10%) and, to a minor degree, into the bone marrow. The RES consists of phagocytic cells originating from the bone marrow. The cells exist in the whole body, but their highest concentration is found in the liver (Kupffer cells), spleen, and bone marrow. Despite their great usefulness to target the brain, because of their high uptake by the RES after intraveneous injection, only a limited proportion of the nanoparticles actually reach the brain [97, 98]. Unless their surface is modified by special coatings (described below), nanoparticles themselves are of little value for delivery of drugs to the brain.
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