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

Nanomedicine. 2019 Apr:17:359-379. doi: 10.1016/j.nano.2019.01.016. Epub 2019 Feb 10.

Abstract

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 nanosystem 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.

Keywords: Blood-brain barrier; Brain pathology; Extracellular matrix; Nanomedicine; Neuropharmacology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / pathology
  • Brain Diseases / drug therapy*
  • Brain Diseases / metabolism
  • Brain Diseases / pathology
  • Delayed-Action Preparations / metabolism*
  • Drug Delivery Systems / methods
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • Humans
  • Nanoparticles / metabolism*
  • Neuropharmacology

Substances

  • Delayed-Action Preparations