Drug delivery to the central nervous system by polymeric nanoparticles: What do we know?

Nanoparticles enable the delivery of a great variety of drugs including anticancer drugs, analgesics, anti-Alzheimerʹs drugs, cardiovascular drugs, protease inhibitors, and several macromolecules into the brain after intravenous injection of animals. The mechanism of the nanoparticle-mediated drug transport across the BBB appears to be receptor-mediated endocytosis followed by transcytosis into the brain or by drug release within the endothelial cells. Modification of the nanoparticle surface with covalently attached targeting ligands or by coating with certain surfactants that lead to the adsorption of specific plasma proteins after injection is necessary for this receptor-mediated uptake. A very critical and important requirement for nanoparticulate brain delivery is that the employed nanoparticles are biocompatible and, moreover, rapidly biodegradable, i.e. over a time frame of a few days. In addition to enabling drug delivery to the brain, nanoparticles, as with doxorubicin, may importantly reduce the drugʹs toxicity and adverse effects due to an alteration of the body distribution. Because of the possibility to treat severe CNS diseases such as brain tumours and to even transport proteins and other macromolecules across the blood–brain barrier, this technology holds great promise for a non-invasive therapy of these diseases.