Delivery of liposomes generated from proliposomes using air-jet, ultrasonic, and vibrating-mesh nebulisers

In this study, particulate-based proliposomes were investigated as a formulation which would form, an isotonic liposome dispersion in situ when nebulised within a medical nebuliser. Transmission electron microscopy and particle size analysis indicated that liposomes were generated from soyaphosphatidylcholine/cholesterol/sucrose proliposomes in air-jet (Pari LC Plus), ultrasonic (Liberty) and vibrating-mesh (Omron NE- U22) nebulisers, without the need for a prolonged hydration step. With jet and vibrating-mesh nebulisers, liposomes were efficiently delivered to the second (lower) stage of a two-stage impinger, indicating such liposomes would be predicted to be delivered to the peripheral airways. Phos- pholipid output from these nebulisers was less than the total mass output, suggesting some accumulation of liposomes in the nebuliser reservoir. The ultrasonic nebuliser delivered less than 6% of available phospholipid to the impinger, demonstrating that this device was inappropriate for delivering a therapeutic proliposome formulation for pulmonary administration. These results show that proliposomes offer a means of producing stable formulations which can readily generate isotonic liposome formulations in situ for delivery to the airways using either an air-jet or vibrating-mesh nebuliser.