In vivo and in vitro assessment of baseline blood-brain barrier parameters in the presence of novel nanoparticles.
OBJECTIVE
Nanoparticles have advantage as CNS drug delivery vehicles given they disguise drug permeation limiting characteristics. Conflicting toxicological data, however, is published with regard to blood-brain barrier integrity and gross mortality.


METHODS
To address this issue two novel nanoparticle types: "emulsifying wax/Brij 78" and "Brij 72/Tween 80 nanoparticles were evaluated in vivo for effect on cerebral perfusion flow, barrier integrity, and permeability using the in situ brain perfusion technique. Additional evaluation was completed in vitro using bovine brain microvessel endothelial cells for effect on integrity, permeability, cationic transport interactions, and tight junction protein expression.


RESULTS
In the presence of either nanoparticle formulation, no overall significant differences were observed for cerebral perfusion flow in vivo. Furthermore, observed in vitro and in vivo data showed no statistical changes in barrier integrity, membrane permeability, or facilitated choline transport. Western blot analyses of occludin and claudin-1 confirmed no protein expression changes with incubation of either nanoparticle.


CONCLUSIONS
The nanoparticle formulations appear to have no effect on primary BBB parameters in established in vitro and in vivo blood-brain barrier models.
Lockman
Paul R
PR
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University HSC, 1300 So. Coulter Dr., Amarillo, Texas 79106-1712, USA.
Koziara
Joanna
J
Roder
Karen E
KE
Paulson
Jennifer
J
Abbruscato
Thomas J
TJ
Mumper
Russell J
RJ
Allen
David D
DD
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size
D004337:Drug Carriers