INCORPORATION OF ALPHA-TOCOPHEROL IN LIPOSOMES PROMOTES THE RETENTIONOF LIPOSOME-ENCAPSULATED GLUTATHIONE IN THE RAT LUNG

The present study was undertaken to investigate whether oc-tocopherol incorporated in liposomes could improve the retention of entrapped glu tathione (GSH) in the lung following intratracheal instillation in rat s. Rats were treated with a single dose of [H-3]GSH entrapped in lipos omes with or without 30 mol% alpha-tocopherol and killed 0, 24 or 48 h later. The retention of GSH in the lung was assessed by measuring the recovery of either H-3-label or GSH in the lung. Animals instilled wi th free [H-3]GSH were found to retain only 2% of the administered dose at 24 h after treatment and no detectable radioactivity at 48 h. Lipo some encapsulation altered the pulmonary retention of GSH with 18 and 10% of radioactivity remaining in the lung at 24 and 48 h post-treatme nt, respectively. The instillation of GSH encapsulated in alpha-tocoph erol-containing liposomes resulted in the highest level of GSH retenti on in the lung, namely 37 and 30% of the administered GSH dose at 24 a nd 48 h, respectively. Results from Sepharose 4B column chromatography revealed that lung homogenates, obtained from rats instilled with GSH entrapped in alpha-tocopherol-containing liposomes, 24 and 48 h earli er, contained 2 eluted GSH-related components-one associated with the liposomal lipid marker in the void volume and the other as free GSH tr ipeptide, suggesting a slow sustained release effect mediated by the l iposomal formulation. The same liposome preparation containing both al pha-tocopherol and GSH also conferred better protection against FeADP- induced lipid peroxidation than liposomes containing either alpha-toco pherol or GSH alone, indicative of a potentially effective antioxidant formulation for treating oxidative lung injury.