Insights into Infusion-Based Targeted Drug Delivery in the Brain: Perspectives, Challenges and Opportunities

Abstract

Targeted drug delivery in the brain is instrumental in the treatment of lethal brain diseases, such as glioblastoma multiforme, the most aggressive primary central nervous system tumour in adults. Infusion-based drug delivery techniques, which directly administer to the tissue for local treatment, as in convection-enhanced delivery (CED), provide an important opportunity; however, poor understanding of the pressure-driven drug transport mechanisms in the brain has hindered its ultimate success in clinical applications. In this review, we focus on the biomechanical and biochemical aspects of infusion-based targeted drug delivery in the brain and look into the underlying molecular level mechanisms. We discuss recent advances and challenges in the complementary field of medical robotics and its use in targeted drug delivery in the brain. A critical overview of current research in these areas and their clinical implications is provided. This review delivers new ideas and perspectives for further studies of targeted drug delivery in the brain.

Keywords: brain; convection-enhanced delivery; fluid flow; infusion; mass transport; molecular interactions; tissue deformation.

Figure 1

The CNS components that offer major resistance to drug flow and distribution.

Figure 2

Extracellular matrix (ECM) components are arranged into basement membranes that lie outside cerebral vessels, condensed as perineuronal nets around the cell bodies and dendrites of neurons or diffusely distributed as the neural interstitial matrix between cells of the CNS parenchyma. The pink glial cells depict astrocytes, oligodendrocytes or microglia. This figure has been reproduced from [80] with permission from Springer Nature.

Figure 3

Schematic representation of macro- and microscale deformation of brain parenchyma during infusion.