Lung retention of phosphatidylcholine and cholesterol from liposomes: effects of oxygen exposure and fasting.
Antioxidants such as glutathione may play a role in prevention and treatment of several lung diseases. Liposomes can be used to deliver antioxidants to the lung and increase their retention. In addition, liposomes alone may protect against oxidant-induced damage. In addition, liposomes alone may protect against oxidant-induced damage. This study was designed to characterize the retention and distribution of liposomes in the lung under normal circumstances and during either fasting, exposure to 100% oxygen, or a combination of the two. Positively charged liposomes, consisting of phosphatidylcholine (PC), cholesterol, and stearylamine plus either [14C]cholesterol or [3H]PC, were instilled intratracheally. Five minutes to 5 days later the lungs were removed and the radioactivity determined. Both [14C]cholesterol and [3H]PC labels had prolonged and equal retention in the lung, but their distribution within lung compartments differed. The cholesterol label increased in lung tissue over time, comprising 78% of the remaining label after 5 days, whereas the PC label persisted at high levels in lavage fluid and became equally distributed between lung tissue and bronchoalveolar lavage fluid. Fasting had little effect on the retention of the labels and no effect on their distribution within the lung. Exposure to 100% oxygen increased lung retention of both radiolabels and altered their distribution such that [14C]cholesterol label decreased and [3H]PC label increased in lung tissue. These results demonstrate the prolonged retention of intratracheally administered liposomes or their components in the lung and the effects of two clinically relevant conditions, fasting and hyperoxic exposure. Furthermore, they provide a basis for designing future studies using liposomes.
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
L J
LJ
Smith
J
J
Anderson
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D002784:Cholesterol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005215:Fasting; D008081:Liposomes; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D008081:Liposomes; D010713:Phosphatidylcholines; D002784:Cholesterol; D010100:Oxygen