Targeted delivery across the blood-brain barrier.
The safest and most effective way of targeting drugs to the entire brain is via delivery systems directed at endogenous receptor-mediated uptake mechanisms present at the cerebral capillaries. Such systems have been shown to be effective in animal models including primates, but no clinical trials have been performed so far. This review focuses on the well-characterised transferrin and insulin receptor-targeted systems, as well as on the more recently described systems that use the low-density lipoprotein-related protein 1 receptor, the low-density lipoprotein-related protein 2 receptor (also known as megalin and glycoprotein 330) or the diphtheria toxin receptor (which is the membrane-bound precursor of heparin-binding epidermal growth factor-like growth factor). The possibilities and limitations of these systems are compared and their future for human application is discussed.
Gaillard
Pieter J
PJ
to-BBB technologies BV, Bio Science Park Leiden, Gorlaeus Laboratories, LACDR Facilities-FCOL, The Netherlands. Gaillard@toBBB.com
Visser
Corine C
CC
de Boer
Albertus G
AG
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000502:physiology; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011990:Receptors, Transferrin / Q000737:chemistry / Q000378:metabolism
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D004364:Pharmaceutical Preparations; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D011972:Receptor, Insulin