Nebulization of liposomes. I. Effects of lipid composition.

A series of multilamellar liposome dispersions was prepared from lipids of soy phosphatidylcholine or hydrogenated soy phosphatidylcholine containing from 0 to 30 mol% of either cholesterol, stearylamine, or dipalmitoyl phosphatidylglycerol. The liposome dispersions were aerosolized with a Collison nebulizer for 80 min at an output flow rate of 4.7 liters of air/min. The effects of nebulization on the vesicles were determined by monitoring the release of encapsulated 5,6-carboxylfluorescein (CF) from dispersions containing approximately 200 micrograms of total CF, of which 93.1 +/- 2.4% (N = 18) was initially encapsulated. In all experiments CF was released from the liposomes while being aerosolized, and this ranged from a mean of 12.7 +/- 3.8 to 60.9 +/- 1.9% of the encapsulated CF, depending upon the lipid composition. The lipid concentration in the dispersions did not affect the rate or percentage release of CF over a range of approximately 0.5 to 50 mg per nebulized dispersion. If liposomes are to be used as drug carriers in an inhalation aerosol a lipid composition should be employed which will minimize the release of encapsulated drug caused by nebulization.