Laser diffraction and electron microscopy studies on inhalable liposomes generated from particulate-based proliposomes within a medical nebulizer

Particulate-based proliposomes were made by coating sucrose carrier particles with egg phosphatidylcholine (EPC), soya phosphatidylcholine (SPC) or soya phosphatidylcholine with an equimole ratio of cholesterol (SPC:Chol, 1:1). Inhalable multilamellar liposomes were generated from proliposomes in situ within a Pari LC Plus nebulizer by addition of aqueous phase, with no need for prior manual shaking. All proliposome formulations produced high aerosol and phospholipid outputs and were delivered in high fractions to the lower stage of a two-stage impinger. The SPC:Chol (1:1) liposomes tended to accumulate more in the nebulizer because of their greater rigidity, which correlated with the larger size measured at the end of nebulization. The size of aerosol droplets as measured by laser diffraction was similar for all formulations, however, at the sputtering period, the SPC:Chol (1:1) formulation produced large droplets with broadened size distribution. This study has demonstrated a simple approach to delivering high outputs of liposomes using a particulate-based proliposome technology and has shown an evidence of liposome generation from proliposomes within a medical nebulizer.