Abstract

Strategic Drug Delivery Targeted to the Brain: A Review

The central nervous system (CNS), efficiently isolated from the systemic circulation by the blood–brain barrier (BBB), represents a challenging therapeutic target. For CNS targeted agents, augmenting brain exposure by increasing blood drug concentrations often is prohibited by systemic toxicity. Therefore, a means for selectively increasing brain exposure, while minimizing systemic exposure, would be desirable. 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. Although several promising molecules have the potential in the in vitro settings but lack of in vivo response is probably because the molecule cannot reach the brain in a sufficient concentration. Drug delivery across the BBB is a major limitation in the treatment of central nervous system (CNS) disorders and CNS infections. As pharmacological strategies improve, there will be less need for invasive procedures for treating CNS diseases. Considerable strides have been made in intravascular delivery and neurosurgical invasive procedures to deliver therapeutic substances into the brain. This review deals with the role of several strategies and rational drug design directed at delivering drugs to the brain.


Author(s): Sandipan Roy

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