Nanoparticle-Derived Non-Viral Genetic Transfection at the Blood-Brain Barrier to Enable Neuronal Growth Factor Delivery by Secretion from Brain Endothelium

L.      B. Thomsen; A.      B. Larsen; J.      Lichota; T.      Moos

Abstract

Brain capillary endothelial cells form the blood-brain barrier (BBB) that denotes a major restraint for drug entry to the brain. The identification of many new targets to treat diseases in the brain demands novel thinking in drug design as new therapeutics could often be proteins and molecules of genetic origins like siRNA, miRNA and cDNA. Such molecules are otherwise prevented from entry into the brain unless encapsulated in drug carriers. The desirable entry of such large, hydrophilic molecules should be made by formulation of particular drug carriers that will enable their transport into the brain endothelium, or even through the endothelium and into the brain. This manuscript reviews the potential of different drug-carriers for therapy to the brain with respect to their targetability, biocompatibility, toxicity and biodegradability.

Keywords: Blood-brain barrier, Drug delivery, Lipoplexes, Magnetic nanoparticles, Nanoparticle, Polyplexes, Pullulan, Transferrin receptor, hydrophilic molecules, endothelium