Morphology and bilayer integrity of small liposomes during aerosol generation by air-jet nebulisation
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Small liposome suspensions (hydrodynamic diameter, 80–130 nm) were nebulised, and the resulting changes in morphology and bilayer integrity were found to be related to surface properties controlled by bilayer composition. Four separate liposome compositions (or liposome types) were investigated using three different phospholipids with unique properties. Morphological changes were studied using light scattering and imaging of liposomes before and after nebulisation, and structural integrity was investigated on the basis of the retention of an encapsulated dye (probe molecule). Nebulisation generated droplets contained liposomes. The liposome particles generated on droplet evaporation had a hollow structure as evidenced by electron imaging, indicating that the lipid bilayer does not collapse on evaporation. The particles of all compositions had mobility diameters between 50 and 90 nm, 1.4–1.6 times smaller than their diameters (hydrodynamic) measured before nebulisation, implying considerable volume shrinkage. Liposomes that had polymer-conjugated lipids covering their external surface underwent aggregation during nebulisation, evidenced by increased diameter after nebulisation. Incorporation of charged lipids reduced nebulisation-induced aggregation, but induced greater membrane rupture during aerosol generation, causing leakage of encapsulated probe molecules. Incorporation of both cholesterol and charged lipids prevented aggregation, but also preserved bilayer integrity, evidenced by the maximum retention of encapsulated dye observed in these conditions (>85%). The findings suggest that liposome bilayer composition can be manipulated to improve the efficiency of liposome aerosol delivery.
KeywordsStability Aggregation Mobility diameter Rupture Dye retention Nanoparticles Lung drug delivery
- Anabousi VS (2006) Liposomal drug carrier systems for inhalation treatment of lung cancer. der Universität des Saarlandes, SaarbrückenGoogle Scholar
- Behr J, Zimmermann G, Baumgartner R, Leuchte H, Neurohr C, Brand P, Herpich C, Sommerer K, Seitz J, Menges G, Tillmanns S, Keller M, Grp MLT (2009) Lung deposition of a liposomal cyclosporine A inhalation solution in patients after lung transplantation. J Aerosol Med Pulm Drug Deliv 22(2):121–129. doi:10.1089/jamp.2008.0714 CrossRefGoogle Scholar