In collaboration with colleagues from the RIBBDD research initiative, supported by the Lundbeck Foundation, researchers at DTU Health Tech have uncovered new possibilities for delivering drugs into the brain.
A tight layer of cells, forming the so-called blood-brain barrier, surrounds and protects our brain. This barrier effectively regulates the molecular transport from the blood into the central nervous system, for example, preventing the passage of pathogens such as infectious agents or germs.
The barrier is thus of critical importance for human function and health. At the same time, however, it restricts the access of many current therapies to the brain, creating an obstacle for effective treatment of several neurological disorders.
The scientific community has tried to solve this issue using numerous different drug carriers to transport medicine across the barrier, but so far, only with modest success. This calls for a better mechanistic understanding of the blood-brain barrier.
A feasible route for delivering drugs into the brain
“In our study, we have used advanced fluorescence microscopy to collect further knowledge about the blood-brain barrier. Imaging through a small hole in the skull directly into the brain of living mice, we investigated the interactions of common nanoparticle drug carriers with the blood-brain barrier,” Researcher Kasper Kristensen, who was part of the research team at DTU, explains.
This specific imaging method provided unique insights into the interactions between nanoparticles and the blood-brain barrier through high-resolution images in real time.
The key conclusion reached by the research team was that post-capillary venules i.e. the very small blood vessels at the blood-brain barrier are the point-of-least resistance and provide a more feasible route for nanoparticle drug carriers into the brain.
Postdoc Kasper Bendix Johnsen, who was also part of the research team, finishes, “In addition to giving a wealth of new information about the movements of the nanoparticles at the barrier, our results demonstrate that nanoparticle translocation across the barrier into the brain occurs only in distinct vascular segments. This is possibly because these segments are surrounded by a fluid space that provides room for the nanoparticles”.
This insight is of fundamental importance for future design and development of drug delivery systems targeting the brain, potentially facilitating the treatment of hitherto untreatable neurological conditions such as Parkinson's, Alzheimer's, and Huntington's disease.
Read the full paper in Nature Communications
Top image: The brain has a very complex network of blood vessels that secures the needed nourishment to the brain, and constitutes the so-called blood-brain barrier, which makes it impossible for most drugs to enter the brain. (Image by Serhii Kostrokov)
The work has been carried out within the framework of the ‘Research Initiative on Brain Barriers and Drug Delivery (RIBBDD)’.
The aim of RIBBDD is to provide new tools for drug delivery across the BBB.
The project is headed by Professor Martin Lauritzen, University of Copenhagen.
Principal Investigators include:
- Professor Thomas L. Andresen, Technical University of Denmark
- Associate Professor Morten Schallburg Nielsen, Aarhus university
- Professor Torben Moos, Aalborg University
- Professor Birger Brodin, University of Copenhagen
- Professor Kristian Strømgaard, University of Copenhagen
RIBBDD is a strategic project funded by the Lundbeck Foundation in 2014 (40 MDKK). The initiative was extended twice, in 2016 for two years (20 MDKK) and in 2018 for two years (24 MDKK).