Negative :

1 : 3.5

1 : 2.3

1 : 1.8

1 : 3.9

1 : 2.9

1 : 28.0

zwitterionic lipid ratio (exclusive of CHO and TG)

zwitterionic lipid ratio (exclusive of CHO and TG)

"The %w/w values in this table for BBB and MDCK are conversions from the originally reported %mol/ mol units.

bPC = phosphatidylcholine, PE = phosphatidylethanolamine, PS = phosphatidylserine, PI = phosphati-

dylinositol, Sph = sphingomyelin, FA = fatty acid, PA = phosphatidic acid, LPI = lyso-PI, CL = car-

diolipin, LPC = Iyso-PC, CHO = cholesterol, CE = cholesterol ester, TG = triglycerides.

cBBM = reconstituted brush-border membrane, rat (average of four studies).

dMDCK = Madin-Darby canine kidney cultured epithelial cells [563].

eBBB = blood-brain barrier lipid model, RBE4 rat endothelial immortalized cell line.

f Refs. 561 and 562.

gFrom Avanti Polar Lipids, Alabaster, AL.

^Unspecified neutral lipid, most likely asymmetric triglycerides.

the unstirred water layer (UWL; see Section 7.7.6) may be neglected (as, e.g., in the GIT and the BBB) [536,558,559]. The pH effects of ionizable molecules is illustrated in Fig. 7.12, for a series of weak acids and bases [562]. It is clear that if the 'wrong' pH is used in screening the permeabilities of molecules, highly promising molecules, such as furosemide or ketoprofen (Fig. 7.12), may be characterized as false negatives. The ideal pH to use for in vitro screening ought to reflect the in vivo pH conditions.

Said et al. [78] directly measured the ''acid microclimate" on the surface of gastrointestinal tract (GIT) epithelial cells (intact with mucus layer) in rats. The pH on the apical (donor) side of the cells varied from 6.0 to 8.0, while the pH on the basolateral (acceptor) side was 7.4. Furthermore, the pH gradient between

0 0

Post a comment