Phospholipid bilayer permeability of .BETA.-lactam antibiotics.

Publisher Website
Google Scholar
Abstract
Liposomes containing penicillinase or cephalosporinase were prepared from the phospholipids of Escherichia coli. After free .beta.-lactamase was inactivated by clavulanic acid or penicillanic acid sulfone followed by separation of inactivated enzyme and inhibitor from liposomes by gel filtration, the permeability of these liposomes to ampicillin, cefazolin and cephaloridine was estimated by measuring the hydrolysis of these antibiotics by the entrapped enzymes. The permeability parameter C (min-1 .mu.M lipid-1) of ampicillin, cefazolin and cephaloridine was 2.35 .times. 10-4, 0.33 .times. 10-4 and 0.52 .times. 10-4, respectively. The lipid bilayer permeability of these antibiotics was also measured by using liposomes containing these antibiotics. About 1/2 of the initially entrapped ampicillin was released from the liposomes within 80 min, no significant release of cefazolin and cephaloridine was detected during the same period. Thus, the lipid bilayer membrane is more permeable to ampicillin than to cefazolin and cephaloridine. This may explain why ampicillin is a more effective antibacterial drug than cefazolin and cephaloridine against porin-deficient mutants.