Nebulization of liposomes. II. The effects of size and modeling of solute release profiles.

A series of carboxyfluorescein (CF)-containing multilamellar vesicle (MLV) dispersions was prepared and extruded through polycarbonate membranes ranging in size from 0.2 to 5 microns. Vesicle dispersions were nebulized for 80 min using a Collison nebulizer, and the release of CF was monitored during nebulization. Solute retention was dependent upon the size of the vesicles and leakage ranged from 7.9 +/- 0.4% (N = 3) for vesicles extruded through 0.2-microns filters to 76.8 +/- 5.9% (N = 3) for liposomes that were not filtered. Solute release profiles obtained over greater than or equal to 420-min nebulization periods conformed to a two-compartment kinetic model and exhibited a "fast" initial phase (k1 = 0.052 +/- 0.0043) followed by a "slow" terminal phase (k2 = 0.0034 +/- 0.00018). The results show that CF retention can be increased by nebulizing small vesicles and modeling suggests that the rate of CF leakage from the bilayers is faster than from the core of the liposomes.