The blood-brain barrier (BBB) is formed by the special nature of the endothelial cells of the brain capillaries characterized by tight junctions between cells and a high expression of efflux pumps only allowing the brain access to nutrients necessary for cell survival and function. These properties of the BBB result in the incapacity of small and large therapeutic compounds to reach the brain at therapeutic concentrations. Various strategies are now being developed to enhance the amount and concentration of these compounds in the brain parenchyma. The development of new technologies such as peptide vectors has the potential to achieve the delivery of active agents in therapeutic concentrations across the BBB to treat brain diseases such as brain primary and metastatic cancers and neurodegenerative disorders. In this review, the design of new active peptides and development of new peptide vectors for drug brain delivery using physiological approaches will be addressed. A new chemical entity incorporating angiopep peptide in a small anticancer agent (paclitaxel) is now in clinical trials. It is the first of such designed agents to be validated for the treatment of human brain cancers and opens the door for such approaches.
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