Nanoparticles as a Tool to Overcome the Blood-Brain Barrier

摘要

The blood-brain barrier (BBB) prevents the deliveryof most drugs to the central nervous system(CNS). A promising possibility to overcome thisproblem is a delivery by nanoparticles. Drugs thathave been transported into the brain and led to significantpharmacological effects after intravenousinjection using nanoparticles include the hexapeptidedalargin, nerve growth factor (NGF), loperamide,tubocurarine, doxorubicin, the NMDA receptor antagonistsMRZ 2/576 and MRZ 2/596, and others. Inorder to achieve a significant transport across theBBB, coating of the nanoparticles with polysorbate80 (Tween(R) 80) or poloxamer 188 (Puronic(R) F 68) orthe attachment of targeting ligands such as apolipoproteinA-1 or E, transferrin or certain antibodies isnecessary. Nanoparticles loaded with doxorubicinenabled a long term survival for 6 months of up to 40% of rats after intravenous injection in the extremelyaggressive glioblastoma 101/8 model transplantedintracranially, whereas the controls died between 10– 20 days. The mechanism for the nanoparticlemediatedtransport of the drugs across the BBBappears to be endocytosis by the endothelial cellslining the brain blood capillaries and, possibly, transcytosis.