The blood-brain barrier and beyond: Nano based neuropharmacology and the role of extracellular matrix.

Restrained drug delivery due to the blood-brain barrier (BBB) considerably limits options for the treatment of brain pathologies. The utilization of nanoparticulate (NP) carriers has been proposed as a solution. The development strategies need to address the important hurdle of NP passage across the BBB as well as the altered cellular up-take due to the pathophysiological changes of the damaged or diseased tissue as well as immunological and toxicological aspects of nanomedicine penetration. This review therefore scopes to: 1] outline the state-of-the art knowledge on BBB passage, 2] address the significant influence of pathological conditions on nanoparticulate drug delivery, and, 3] highlight the largely neglected role of the extracellular matrix (ECM). Interactions of the nano-system with biological barriers, cells and ECM in the milieu of brain pathologies are critically discussed in order to present a holistic overview of the advances and pits of nanomedicine applications in brain disease.