Drug targeting to the brain

Many brain diseases (such as meningitis, encephalitis, multiple sclerosis (MS), stroke, brain tumors, epilepsy, Alzheimer's disease, AIDS related dementia, Parkinson's disease) are under treated or cannot be treated at all due to the presence of the barriers in the brain (blood-brain barrier, blood-cerebrospinal fluid barrier and the braincerebrospinal fluid barrier). The blood-brain barrier is facing the blood side and is the largest barrier for transport of macromolecular drugs from blood to brain. Therefore, targeting strategies to the BBB are necessary to selectively and specifically transport macromolecular drugs to the brain. This can be accomplished by exploiting receptormediated transport (RMT) systems at the blood-brain barrier. Moreover, enhanced selectivity can be obtained by targeting transport systems induced during disease conditions. Macromolecular protein drugs can be directly linked to a carrier molecule that fits to a RMT system. However, such applications often result in decreased activity of the resulting (fusion) protein and are prone to induce activation of and subsequent degradation by the immune system. Therefore, liposomal systems coated with carrier molecules are an alternative to deliver macromolecular protein drugs to the brain by targeting them to the blood-brain barrier.