ABSTRACT
Many classical treatments of central nervous system (CNS) disease do not access the brain parenchyma owing to the presence of the blood-brain barrier (BBB), which separates the blood compartment from the extracellular fluid compartment of the CNS. The same problem exists in medical imaging for the delivery of diagnostic agents to the CNS (1). The BBB is made up of endothelial cells that form very occlusive tight junctions (2). It is widely accepted that only compounds that are unionized at physiological pH, lipophilic, and of low molecular weight can cross the BBB (3). However, the physico-chemical properties of most drugs (size, solubility, charge, etc.) mean that most of them cannot cross this natural barrier. Furthermore, low pinocytic vesicular traffic and efficient efflux mechanisms in the BBB contribute to failure of treatment (4-6). More than 98% of all potential drugs targeted to the brain do not cross the BBB (7). Consequently, various strategies, reviewed in Temsamani et al. (8) have been explored for drug delivery across the BBB. These include BBB disruption, hyperosmotic shock, administration of vasoactive substances, direct intraventricular drug administration, microparticle implantation, drug modification, receptor-mediated
transcytosis, and peptide-vector strategies (9-16). The present article focuses on non-viral strategies that imply colloidal drug delivery systems (DDSs).
