Polymer nanomaterials

Abstract

The blood brain barrier (BBB) is one of the most challenging barriers for drug delivery in the body. It significantly restricts the entry of low molecular weight compounds and biomacromolecules to the brain from the periphery. Inefficient delivery of the drugs, DNA and proteins to the brain is a major bottleneck in development of more efficacious and safe modalities for diagnostics and treatment of neurological diseases, especially at early stages of the disease when the BBB remains intact. The low permeability of the BBB is attributed, in large part, to the brain microvessel endothelial cells (BMVEC), which form tight extracellular junctions and have low pinocytic activity (Mayhan, 2001; Pardridge, 2005a). Some relatively lipophilic and low molecular weight substances can transport across the BMVEC by passive diffusion. However, a large number of lipophilic compounds are rapidly effluxed from the brain into the blood by extremely effective drug efflux systems expressed in the BBB (Begley, 1996; Fromm, 2000; Tamai and Tsuji, 2000; Loscher and Potschka, 2005a). These efflux systems include P-glycoprotein (Pgp), Multidrug Resistance Proteins (MRPs), breast cancer resistance protein (BCRP), and the multi-specific organic anion transporter (MOAT). There is also an enzymatic barrier to drug transport in the BMVEC. Activity of many enzymes that participate in the metabolism and inactivation of endogenous compounds, such as γ-glutamyl transpeptidase, alkaline phosphatase, and aromatic acid decarboxylase is elevated in cerebral microvessels (Minn et al., 1991; Abbott and Romero, 1996). These features of the BBB require discovery of new modalities allowing for effective drug delivery to the central nervous system (CNS), which is of great need and importance for treatment of neurodegenerative disorders. © 2008 Springer Science+Business Media, LLC.