Marina Vinnikova

Controlled Modulation of the Blood-Brain and Blood-Tumor Barrier Using Novel Lipid Mimetic Compounds

The blood-brain barrier is a dynamic interface that has important physiological functions of specific and selective membrane transport. However, it also significantly limits the influx and efflux process of many drugs that may potentially be used in managing CNS disorders (Pardridge, 1998). Alternatives to current drug delivery to the brain are being actively sought in the research community. Invasive strategies such as intrathecal administration of chemotherapeutics or intracerebral surgical implants following brain surgery (Kroll, 1998), as well as the transient disruption of the blood brain barrier by hyperosmotic mannitol have been the main therapeutic options (Rapoport, 2000). The latter treatment is often associated with severe side-effects and can lead to acute and chronic neuropathies (Newelt 1989). One approach to solving the blood-brain barrier problem is to use agents that will transiently open the BBB and facilitate entry of a particular drug or agent to the brain (Abbot). Modulation of the BBB with bioactive molecules in contrast to osmotic disruption is appearing as an effective technique. Some limited clinical success has been reported with this approach in the permeation of the BTB with the bradykinin agonist, Cereport (RMP-7) (Emerich, 1998).