|
University of Maryland
Project
Collaborative Research Proposal between
PBL at University of Maryland
and the International Journal Drug Development
BBB PROJECT
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
e-mail: neddingt@rx.umaryland.edu
Tel : 410 706 6710
[ Click for BBB advert]
|
|
