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
The authors thank Dr. Valsamma John Koshy, Research Associate, Indian Institute of Technology, Bombay for helpful discussions. We acknowledge the support of the Li-Chung Lai and Chia-Ying Chiang of Maryland NanoCenter, University of Maryland in some of the imaging. We thank Ms. Shobha Ramagiri, for her help in TEM imaging. S.C. acknowledges partial financial support from the IIT Bombay Center for Nanotechnology and Science, DST for support through IRPHA and Nanomission schemes and the Indo US Science and Technology Forum, New Delhi. S.E. acknowledges partial financial support from the US Fulbright Foundation.
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