The brain is a delicate organ, and evolution built very efficient ways to protect it. Unfortunately, the same mechanisms that protect it against intrusive chemicals can also frustrate therapeutic interventions. Many existing pharmaceuticals are rendered ineffective in the treatment of cerebral diseases due to our inability to effectively deliver and sustain them within the brain. General methods that can enhance drug delivery to the brain are, therefore, of great interest. Despite aggressive research, patients suffering from fatal and/or debilitating central nervous system (CNS) diseases, such as brain tumors, HIV encephalopathy, epilepsy, cerebrovascular diseases and neurodegenerative disorders, far outnumber those dying of all types of systemic cancer or heart disease. The clinical failure of much potentially effective therapeutics is often not due to a lack of drug potency but rather to shortcomings in the method by which the drug is delivered. Treating CNS diseases is particularly challenging because a variety of formidable obstacles often impede drug delivery to the brain and spinal cord. By localizing drugs at their desired site of action one can reduce toxicity and increase treatment efficiency. In response to the insufficiency in conventional delivery mechanisms, aggressive research efforts have recently focused on the development of new strategies to more effectively deliver drug molecules to the CNS. This review intends to detail the recent advances in the field of brain-targeting, rational drug design approach and drug delivery to CNS. To illustrate the complexity of the problems that have to be overcome for successful brain targeting, a brief intercellular characterization of the blood–brain barrier (BBB) is also included.
Drug delivery, Nervous system, Prodrug
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