We want to check a new compound whether it crosses the blood brain barrier so that we can used to treat the brain cancer i.e. glioma .
By which techniques or method we identify that particular compound crossing the blood brain barrier or not?
Microdialysis could help you to analyze the efficacy of the drug delivery.
Moreover Magnetic resonance spectroscopy is non-invasive imaging that can be used to assess neurometabolite alterations before and after treatment.
Ref:
Pharmacokinetics of BPA in gliomas with ultrasound-induced blood-brain barrier disruption as measured by microdialysis, DOI: 10.1371/journal.pone.0100104
Application of NMR spectroscopy in medicinal chemistry and drug discovery
DOI: 10.2174/156802611793611850
You can either use in vitro models, e.g., BBB endothelial cell monolayers for permeation studies, or perform in vivo brain uptake studies with subsequent separation of the vascular and tissue fraction of the brain before analyzing compound content
In general, a small lipophilic molecule that is not a substrate of P-gp will likely cross BBB.
I'd measure drug's level in the brain using HPLC,UPLC, or LC/mass/mass, depending on your lab's available toolbox. You'll get better results if you perfuse organs before collection using PBS to avoid mistaking the drug present in the cerebral vasculature for that which extravasated into the brain tissue.
Gert Fricker , can you share any publish paper in which pharmokinetics of compound studied by any in vivo brain uptake studies.
Pharm Res. 2011 Mar;28(3):456-71
J Cardiovasc Pharmacol . 1993 Feb;21(2):339-46.
Biopharm Drug Dispos. 2010 May;31(4):243-52.
AJ .Kastin and WA Banks have developed the methodology and used it for the last 30 years with many and many papers published.
Essentially you should label the compound, and: 1) administer it centrally using the intracerebroventricular route and then follow it peripherically; 2) ou administer it perifpherally generally the intraperitoneally route and then follow it centrally with the sacrifice of the animal and brain collection. Mice and rats can be used.
sincerely yours and good luck
João Martin Martins
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