Morphology and bilayer integrity of small liposomes during aerosol generation by air-jet nebulisation |
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Authors: | Saptarshi Chattopadhyay Sheryl H Ehrman Jayesh Bellare Chandra Venkataraman |
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Institution: | (1) Department of Chemical Engineering, Indian Institute of Technology-Bombay, Powai, Mumbai, 400076, India;(2) Centre for Research in Nanotechnology and Science, Indian Institute of Technology Bombay, Mumbai, India;(3) Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD, USA; |
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Abstract: | 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. |
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