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Abstract

Previously our laboratory (Rim et al., Int. J. Pharm. 32:79-84. 1986) described an in vitro blood-brain barrier (BBB) model consisting of cultured bovine brain microvessel endothelial cells (BMECs) grown onto regenerated cellulose acetate membranes. However, the utility of this in vitro BBB model system was limited because the regenerated cellulose acetate membrane and not the monolayer of bovine BMECs was rate limiting for the permeability of very lipophilic compounds. Therefore, in this study we have evaluated polycarbonate membranes as supports for growing bovine BMECs and for conducting in vitro drug permeability studies. Bovine BMECs were cultured on collagen-coated polycarbonate membranes (13-mm diameter, 12-microns pore size) which were then mounted into side-by-side diffusion cells for transport studies. The permeabilities of a series of solutes of varying lipophilicity (progesterone, estrone, testosterone, haloperidol, propranolol, antipyrine, caffeine, urea, acyclovir, ganciclovir, ribavirin, and glycerol) were determined and an excellent correlation (r = 0.97) was established between the permeability coefficients of the solutes and their log partition coefficients (PC)/(MW)1/2. These results suggest that bovine BMECs cultured onto polycarbonate membranes can be used as an in vitro model system for estimating the potential permeability of a solute through the BBB in vivo.

The blood-brain barrier: an engineering perspective

“…A solute, typically radio-labeled or fluorescently-labeled, is introduced into the input chamber and the amount accumulated in the output chamber is measured as a function of time, typically over a period of 1–2 h (Bowman et al, 1983; Audus and Borchardt, 1986; Shah et al, 1989; Karlsson and Artursson, 1991; Artursson, 1991; Freed et al, 2001; Chappa et al, 2006; Summerfield et al, 2007). The concentration of solute on the input side c in (mol cm −3 ) and the area A (cm 2 ) of the monolayer are the input parameters, and the concentration of solute on the output side is measured as a function of time.…”

Analytical and Biological Methods for Probing the Blood-Brain Barrier

“…One of the simplest methods to determine the transport of compounds across the BBB is the use of radiolabeled compounds and scintillation counting (84, 85). Scintillation counting is frequently employed in competitive studies that are performed to determine whether saturable, carrier-mediated processes are responsible for a compound's permeation.…”

QSAR Studies on Blood-Brain Barrier Permeation

“…For example, Shah et al [76] It should be noted that a significant correlation was also obtained when both log Poct and log Mw were used as independent variables instead of the molecular weight function (r 2 = 0.908) [61].…”