Size Distribution and Morphology of Liposome Aerosols Generated By Two Methodologies

Pulmonary delivery of sustained release formulations needs drug encapsulation in a suitable matrix, as well as the generation of aerosols with high lung penetration and suitable release characteristics. Nanometer sized liposomes offer the potential for biocompatibility, controlled release and easy internalization in the lung. For uniform dose delivery and drug release kinetics, it is of interest to understand generation techniques to obtain aerosols containing nearly monodispered nanometer sized dry particles. Two aerosolization techniques, air-jet atomization and electrohydrodynamic atomization (EHDA) were studied to identify conditions under which the inclusion of one-liposome-per-drop could be achieved. In air-jet atomization, low lipid concentrations resulted in a unimodal aerosol with a median mobility diameter of 94 (+/- 3.5) nm, while higher concentrations led to larger median diameters, implying possible inclusion of multiple liposomes per drop. In EHDA, tuning drop sizes in the range of 130 to 200 nm, as well as the use of high lipid concentrations, resulted in a bimodal aerosol distribution, with peaks at 35 and 100 nm mobility diameters. TEM images of the liposome aerosol from EDHA showed fused liposomes, resulting in cylindrical structures with different physical diameters. It was hypothesized that deformation of liposomes to cylindrical structures in the micro-capillary liquid tip of the electrospray, and interactions along the axial or cross sectional surfaces led to dry particles with different mobility sizes.