Liposomes and bronchoalveolar lavage fluid: Release of vesicle-entrapped glutathione

Abstract

Interest in the potential applications of liposomes for pulmonary drug delivery prompted this in vitro study of the effect of lipid composition on vesicle permeability. Rat cell-free bronchoalveolar lavage fluid was incubated at 37°C with large unilamellar liposomes, prepared by the extrusion technique, containing entrepped [ 3H]glutathione (GSH). Lavage-induced GSH leakage occurred for liposomes prepared from dipalmitoylphosphatidylcholine (DPPC). However, leakage from dimyristoylphosphatidylcholine (DMPC) liposomes in the presence of lavage was not different from leakage in control buffer. Cholesterol was found to enhance GSH release from distearoylphosphatidylcholine (DSPC) adn DPPC vesicles, and to stabilize DMPC visicles. The results suggest that DPPC liposomes may be more suitable than vesicles prepared from DSPC or DMPC for effective delivery of GSH to the lung, and that variation of cholesterol content can be used to enhance selectively or diminish the in-vitro release characterisitics.