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 soya phosphatidylcholine/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. Phospholipid 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.