Advantages and disadvantages of using bovine serum albumin and/or Cremophor EL as extracellular additives during transport studies of lipophilic compounds across Caco-2 monolayers

The effects of Cremophor EL (CEL) and bovine serum albumin (BSA) on the active and passive permeation of BCS class II compounds (felodipine, asimadoline) were studied across Caco-2 cells. The effect of BSA on either or both sides of the monolayers, apically applied CEL in the presence of basolateral BSA and the effect of addition of CEL on P-gp by the use of quinidine were investigated. Presence of 4% BSA improved sink conditions and recovery from 60 to 95% for both felodipine and asimadoline. Efflux ratios obtained under comparable sink conditions, indicated that felodipine was transported by passive diffusion, while quinidine and asimadoline were transported actively. CEL decreased the transport rate for felodipine and asimadoline in the absorptive direction and increased in the secretory direction at different CEL concentrations, most likely due to the incorporation of drug into micelles. Our results indicate that inclusion of BSA is generally sufficient to increase the recovery for lipophilic BCS class II compounds. The overall effect of CEL on the permeability of a drug is compound specific and, therefore, less predictable and cannot be recommended.