Anticancer drug delivery to the brain: outwitting the blood-brain barrier

Brain tumors are responsible for almost 2% of deaths in the Western world. The most used methods nowadays to treat a malignant brain tumor are surgery, radiotherapy and chemotherapy, generally applied in combination. The prognosis for patients suffering from a highly malignant glioblastoma multiforme (GBM), about 25% of all brain tumors, is only 6 months after surgery. This prognosis has remained the same for a long time. After surgery, the tumor often recurs at the resection site. The contribution of chemotherapy to survival of patients suffering from GBM is uncertain, because of failure in delivery of most of the drugs to the brain. The main reason causing this failure is the existence of the blood-brain barrier (BBB), a highly selective barrier between blood and the brain tissue that keeps components like pathogens or undesired molecules outside the brain. For successful drug delivery, the BBB has to be outwitted. This paper reviews three new methods for drug delivery to the brain and gives insight into their efficacy. The methods that are discussed are delivery of drugs by loaded nanoparticles, delivery of biological products by encapsulated cells and disruption of the BBB induced by focused ultrasound. These techniques are not used in clinic yet, but hopefully contribute to better treatment of malignant brain tumors in the near future.