Pulmonary Uptake of Liposomal Phosphatidylcholine

Abstract

Summary: Liposomes prepared with phosphatidylcholine (PC) labeled with [1-¹⁴C]-dipalmitoyl-PC, dicetylphosphate, cholesterol (molar ratio 7:2:1) were injected into the right ear vein of 2-month-old male rabbits. At 5, 60, and 120 min after injection, organs were removed and analyzed for [¹⁴C]-PC. Lung, liver, and spleen took up the [¹⁴C]-PC by 5 min. Spleen accumulation of [¹⁴C]-PC increased steadily, liver plateaued from 1-2 hr, and lung fell rapidly. The uptake of liposomal [¹⁴C]-PC by lung and liver was dependent on the concentration of iv injected liposomal [¹⁴C]-PC. All lung subcellular fractions (lamellar bodies, mitochondria, and microsomes) took up [¹⁴C]-PC. Lamellar body [¹⁴C]-PC was highest at 5 min, and then decreased. Still, on a nmole/mg protein basis, uptake of [¹⁴C]-PC by lamellar bodies was higher than other organelle fractions. Of the radioactivity in lung, 95% was [¹⁴C]-PC even after 2 hr, whereas by 1 hr, 28% of liposomal PC absorbed by liver had been degraded.

Speculation: Neonatal respiratory distress syndrome (RDS) is clearly related to alveolar lining surfactant deficiency. PC is quantitatively the principal phospholipid of that surfactant. If iv injected PC in the form of liposomes (large multilamellar concentric bilayer vesicles) can be taken up by lung lamellar bodies, it is possible that this PC will then be available for release to the alveolar surface. This potentially might become a unique biochemical approach in the therapy of neonatal RDS.

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