Disease infl uence on BBB transport in infl ammatory disorders

During diseases of the central nervous system (CNS), such as Alzheimer’s, Parkinson’s, epilepsy, stroke and multiple sclerosis (MS), the protective function of the blood–brain barrier (BBB) is signifi cantly impaired. The infl ammatory response that is frequently associated with such brain diseases may underlie the loss of the integrity and function of the BBB. Consequentially, the delivery and disposition of drugs to the brain will be altered and may infl uence the treatment effi ciency of CNS diseases. Altered BBB transport of drugs into the CNS during diseases may be the result of changes in both specifi c transport and non-specifi c transport pathways. Potential alterations in transport routes like adsorptive-mediated endocytosis and receptor-mediated endocytosis may affect drug delivery to the brain. As such, drugs that normally are unable to traverse the BBB may reach their target in the diseased brain due to increased permeability. On the contrary, the delivery of (targeted) drugs could be hampered during infl ammatory conditions due to disturbed transport mechanisms. Therefore, the inventory of the neuro-infl ammatory status of the neu-rovasculature (or recovery thereof) is of utmost importance in choosing and designing an adequate drug targeting strategy under disease conditions. Within this chapter we discuss how the function of the BBB can be affected during disease and how this may infl uence the delivery of drugs into the diseased CNS.