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University of Maryland Project

Collaborative Research Proposal between PBL at University of Maryland
and the International Journal Drug Development

Blood Brain Barrier Evaluation of CNS Agents

The University of Maryland has been a leader in drug delivery and pharmacokinetic evaluations for over twenty years. The Pharmacokinetics-Biopharmaceutics Laboratory (PBL) is committed to providing the most innovative methods to examine the in vitro and in vivo blood brain barrier (BBB) permeability of your compounds customized to your needs.
You can rely on the PBL for in vitro and in vivo protocols to study the BBB permeability of your new compounds. We also have extensive experience in HPLC, GC, LC/MS which allows us to quickly identify compounds that may have significant permeability across the BBB vs. those that do not.
The approach here will accelerate your decision making process by providing you relevant information on the drug delivery of your CNS active agents. The PBL provides you many years of combined experience in designing studies to provide the best solution to your needs

In Vitro Blood-Brain Barrier Permeability of CNS active agents:
The transport of select CNS active compounds can be performed using bovine brain microvessel endothelial cells (BBMECs).
These are primary endothelial cells which provide information on the permeability of drugs across the blood-brain barrier. BBMEC cultures have provided a method of investigating various carrier-mediated systems and have allowed a qualitative correlation between permeability characteristics determined within various in situ/in vivo BBB models. Bi-directional transport studies can be performed examining at least two concentrations of the test agents.
Additional transport studies can be performed if the following occurs: efflux of CNS compounds (ratio >2). Additional transport studies can be conducted with inhibitors of P-glycoprotein (e.g., rhodamine 123 or verapamil) and MRP (e.g., indomethacin, fluorascein); and carrier mediated transport is suspected, additional permeability studies will be conducted at alternate concentrations to determine Vmax and km.

In Vitro Blood-Brain Barrier Permeability of CNS active agents:
Your most promising candidates can be further evaluated at the PBL by performing studies in animals (mice, rats) to determine the in vivo permeability of your compounds in the brain as well as certain target sites in the CNS.
Along with information about CNS uptake, we can also provide relevant information concerning the pharmacokinetics and drug metabolism of your most promising compounds. Intravenous pharmacokinetic studies can be performed in mice (or rats) to examine the brain uptake, distribution and pharmacokinetics of CNS agents.
IV doses of select compounds will be administered to mice (or rats) and the animals will be sacrificed at various time points after iv administration. Blood samples will be collected by heart puncture and brains as well as other organs will be excised, and weighed. It may not be a pharmaceutical company's approach to examine the in vivo permeability and drug distribution of all agents used in screening. However, to examine the predictability of the in vitro methods, in vivo studies are required.


University of Maryland, Baltimore
Pharmacokinetics-Biopharmaceutics Laboratory ( PBL)
Director, Natalie D. Eddington, PhD
100 Penn Street
Baltimore, MD 21201, USA
Tel : 410 706 6710

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