The use of liposomes as a model for drug absorption: β-lactam antibiotics

Abstract

Abstract Liposomes were prepared from egg phosphatidylcholine-cholesterol-diacetylphosphate (80: 20: 5) and total lipid extracts of rat intestinal mucosa, and the permeability of the liposomal membrane to eight β-lactam antibiotics was studied by using a dynamic dialysis method. Although all the antibiotics used here are ionized and poorly lipid-soluble at pH 6·5, some of them are orally active and efficiently absorbed from the small intestine. The release rate constants from the aqueous dispersion of drug-entrapped liposomes were approximately in the order of their absorbability. Intestinal lipid liposomes were more permeable to the antibiotics than egg lecithin liposomes and the release rate constants for the drugs from intestinal lipid liposomes were strongly correlative with their absorption rate constants, except for cephalothin and ampicillin, the deviations of which could be explained by their surface activity. It is suggested that lipid components of the intestinal mucosa and the bilayer structure may play an important role in the absorption process of the antibiotics. The validity of liposomes as a model for the intestinal absorption of drugs is also discussed.