Title:Brain Delivery Systems via Mechanism Independent of Receptor-Mediated Endocytosis and Adsorptive-Mediated Endocytosis
Volume: 13
Issue: 12
Author(s): Louiza Bohn Thomsen, Jacek Lichota, Thomas Navndrup Eskehave, Thomas Linemann, Joachim Hog Mortensen, Kristian Gaarn du Jardin and Torben Moos
Affiliation:
Keywords:
Blood-brain barrier, endothelium, gene therapy, magnetic nanoparticle, transferrin, transport, endothelial cells, molecular lipidization, magnetic nanoparticles, genetic origins, central nervous system, drug carriers, solute nutrient carriers, hydrophilic molecule
Abstract: The endothelial cells of the brain form the blood-brain barrier (BBB) that denotes a major restraint for drug entry
to the brain. Traditional attempts to bypass the BBB have been by formulation of drugs with lipophilicity or low molecular
weight designed to enable transport via solute nutrient transporters. The identification of many new targets in the
brain cells form new ways of thinking drug design as modern therapeutics could be proteins and molecules of genetic origins
like siRNA and cDNA that are prevented from entry into the brain unless encapsulated in drug carriers. In many
chronic disorders affecting the central nervous system, the BBB is physically intact which further limits the entry of large
molecules. The desirable entry of such molecules will 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 review discusses the
potential of different principles for drug therapy to the brain with these main emphases on drug transport through the
BBB: i) the effects of molecular lipidization, ii) the involvement of solute nutrient carriers, iii) targeted delivery using
small peptides with high membrane penetrating properties, iv) treatment with magnetic nanoparticles. These different
principles for therapy are also discussed with focus on possibilities of their improvement for targeted delivery to the brain.
