Popis: |
The blood-brain barrier (BBB) determines whether or not a given drug can reach the central nervous system (CNS), either by passive diffusion or through carrier or receptor systems. Initial work focused on the structural and physico-chemical requirements favouring transport across the BBB as related to anatomical and physiological features. Such studies have had a significant effect on the design of CNS-active drugs with improved permeability across the BBB. Progress in pharmacology and neurosciences resulted in greater knowledge of CNS diseases and of potential therapies, but also created the need to develop new strategies to improve drug delivery to the brain. For a long time the BBB was considered to be a physical barrier, mainly represented by the cerebrovascular endothelium; however, transport of drugs to the brain may be limited by the metabolic activity of the BBB. The BBB should be regarded as a dynamic rather than a rigid barrier; it can be influenced by astrocytes and probably also by neuronal and hormonal stimuli, and its properties are also affected by diseases of the CNS. This may offer new strategies for targeting drugs to the brain. |