Lung uptake of liposome-entrapped glutathione after intratracheal administration.
The intratracheal delivery of glutathione (GSH), in liposome-encapsulated form, prolongs retention of the drug in the rat lung. This study has been designed to determine the extent and time-course of pulmonary tissue uptake of administered 14C-labelled liposomes containing [3H]GSH. Liposomes, composed of dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine and distearoylphosphatidylcholine each with or without 30 mol% cholesterol showed a clearance greater than 80% from the bronchoalveolar lavage, 24 h after intratracheal instillation. Lung tissue content of 14C-lipid increased with time: by 72 h, 42-56% of the administered dose was recovered from the tissue. [3H]GSH was present in pulmonary tissue in relatively constant amounts throughout the 72 h, ranging from 14-35% of the administered dose. Vesicles composed of DMPC had a low entrapment for GSH. There were only minor differences in GSH entrapment efficiency and lung tissue uptake between vesicles of the other lipid compositions.
Biosciences Division, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada.
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Jurima-Romet
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Shek
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000378:metabolism; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000032:analysis / Q000378:metabolism; D004134:Dimyristoylphosphatidylcholine / Q000032:analysis / Q000378:metabolism; D004337:Drug Carriers; D005978:Glutathione / Q000008:administration & dosage* / Q000032:analysis / Q000378:metabolism; D007442:Intubation, Intratracheal; D008081:Liposomes; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002250:Carbon Radioisotopes; D004337:Drug Carriers; D008081:Liposomes; D002784:Cholesterol; D005978:Glutathione; D004134:Dimyristoylphosphatidylcholine