Size distribution and dye release properties of submicron liposome aerosols

Abstract

Liposome aerosols have been used in controlled release drug delivery applications like insulin, doxorubicin and ciprofloxacin. Limiting the size distribution to submicron particle sizes could enhance pulmonary targeting. This study assessed the use of simple air-jet nebulisation to produce submicron liposome aerosol powders through control of precursor suspension colloidal properties. Colloidal properties of the suspension and particle type, vis-à-vis payload size and controlled release, were varied by changing liposome type (unilamellar and oligolamellar) and lipid concentration. The effects on powder size-distribution and dye-release properties were studied. The influences of (i) nebulisation forces and (ii) subsequent droplet drying were investigated, on changes induced in controlled release properties of the aerosol powders. Liposome aerosols had similar size-distribution properties (median mobility diameter 0.07–0.16 μm and aerodynamic diameter 0.3–1.0 μm), regardless of liposome hydrodynamic diameter (0.13 and 0.28 μm) and lamellarity (unilamellar and oligolamellar). However, increases in median aerodynamic and mobility diameter, by a factor of 1.5–2, were obtained using changes in lipid mass concentration. Dye release rates were unchanged using wet aerosol collection (impingement), but increased using dry collection by impaction. This implies that drying induces changes in the liposome bilayers, which could lead to leakage of drug payload. We find that suspensions of oligolamellar liposomes are suitable for generation of submicron particles with controlled release properties, because of their larger internal volume (drug loading capacity) and lower disruption (change in dye-release rates) during aerosol generation.