ACTIVE BLOOD-BRAIN BARRIER TARGETING STRATEGIES
The BBB acts as a natural defensive layer to protect the brain from various toxic substances while providing the brain with necessary nutrients for proper functioning . Capillary endothelial cells are partially covered by pericytes, basement membrane, and almost fully covered by astrocytic/glial foot processes, which render the BBB a highly efficient barrier. Approximately 98% of small molecules and nearly 100% of large molecules including genes and proteins are prevented from entering the brain . Fig. 4.2 illustrates various structural components of the BBB.
Figure 4.2 Structural components of the blood—brain barrier. (Republished with permission of Nanda K, Mandava, Patel M, Mitra AK. Advanced Drug Delivery to the Brain: John Wiley and Sons Inc. 2013 [chapter 21], permission conveyed through Copyright Clearance Center, Inc.)
To overcome this challenge, many active targeting strategies have been adopted, which are mainly divided into absorptive-mediated transcytosis (AMT), transporter- mediated transcytosis (TMT), and receptor-mediated endocytosis (RMT) .