Projectdetails

of


Drug Delivery across the Blood-Brain Barrier

Keywords:
drug delivery blood-brain barrier

Researchers:
dr. I.S. Zuhorn

Nature of the research:
cell biology; drug delivery; nanocarriers; blood-brain barrier

Fields of study:
biomaterials cell biology

Background / introduction
The treatment of brain-related diseases is hampered by the presence of the blood-brain barrier (BBB), which actively prevents the entry of therapeutics from the blood into the brain. The main constituent of the BBB is a polarized layer of endothelial cells that physically separates the blood from the brain tissue. Consequently, there is a need for drug delivery vehicles (‘nanocarriers’) that via the principle of a Trojan Horse mediate transendothelial transport of medicines.
Research question / problem definition
For drug delivery into the brain, nanocarriers are being developed that need to:
- be stable in the blood stream;
- release the drug when they reach the brain.
Workplan
Biodegradable and/or stimuli-responsive nanocarriers are made.
Their capacity to cross an in vitro blood-brain barrier and, subsequently, the release of drugs into underlying tissue is measured.
The delivery of hydrophilic (e.g. siRNA) as well as hydrophobic (e.g. small-molecule inhibitors) drugs will be investigated.
References
1. Peptide-mediated blood-brain barrier transport of polymersomes.
Georgieva JV, Brinkhuis RP, Stojanov K, Weijers CA, Zuilhof H, Rutjes FP, Hoekstra D, van Hest JC, Zuhorn IS.
Angew Chem Int Ed Engl. 2012 Aug 13;51(33):8339-42. doi: 10.1002/anie.201202001.
2. In vivo biodistribution of prion- and GM1-targeted polymersomes following intravenous administration in mice.
Stojanov K, Georgieva JV, Brinkhuis RP, van Hest JC, Rutjes FP, Dierckx RA, de Vries EF, Zuhorn IS.
Mol Pharm. 2012 Jun 4;9(6):1620-7. doi: 10.1021/mp200621v.
3. Surface characteristics of nanoparticles determine their intracellular fate in and processing by human blood-brain barrier endothelial cells in vitro.
Georgieva JV, Kalicharan D, Couraud PO, Romero IA, Weksler B, Hoekstra D, Zuhorn IS.
Mol Ther. 2011 Feb;19(2):318-25. doi: 10.1038/mt.2010.236.
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