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The thesis details investigations into the use of various types of medical nebuliser for the generation of liposomal aerosols. Chapter 1 provides a comprehensive introduction to the theory and practice of drug delivery to the respiratory tract. It also reviews the potential applications of inhaled liposomes to drug delivery, and the devices used to generate liposomal aerosols.A preliminary investigation into the physicochemical attributes of liposomes which may. influence aerosol generation is detailed in chapter 2. These include studies of the stability of liposome bilayers to disruptive energy (ie. membrane extrusion and sonication), investigations of the surface tension and viscosity of liposomes, and also the release of a liposomally entrapped hydrophilic marker. Chapter 3 demonstrates how these physicochemical attributes may influence nebulised liposomal aerosols. Most notably, the aerosol droplet size and output rate are proportional to the concentration of the formulation.The residual liposome concentration is determined by the mean liposome size. The droplet size, nébulisation time, aerosol output, and residual liposome concentration are all significantly influenced by the particular jet nebuliser model selected for aerosol generation. The relative stability of different liposome formulations to nébulisation is also determined by a variety of factors, as revealed in chapter 4 of the thesis. The release of an entrapped marker, and the reduction in liposome size during nébulisation, is influenced by the nebuliser model, and also the liposome size and bilayer composition.Chapter 5 investigates the freeze drying of liposomes. The chapter concludes that liposomes for nébulisation may be freeze dried in the presence of a cryoprotectant, without influencing the aerosol produced following subsequent rehydration. Chapter 6 reveals that the droplet size produced from ultrasonic nebulised liposomes is relatively large, and the output inefficient from concentrated formulations. In addition, ultrasonic nébulisation is associated with similar liposome stability concerns as jet nébulisation.

Egg phosphatidylcholine liposomes were freeze-dried in the presence and absence of trehalose. The lyophilized liposomes were rehydrated and aerosolized using a Pari LC jet nebulizer. The size of the aerosols generated was determined by laser diffraction, which was also used to determine the size distribution of the liposomes before lyophilization, post-rehydration, in the nebulizer post-aerosolization and those deposited in the two stages of a twin impinger. In the absence of trehalose, large liposomes and vesicle aggregates were produced on rehydration, which were rapidly reduced in size on nebulization. Liposomes with a mean size of 1 or 2.5 microm, freeze-dried with trehalose, had a mean size less than 3 microm following rehydration and exhibited enhanced stability to nebulization. Liposomes of 1 microm before freeze-drying were evenly distributed within aerosols generated by the nebulizer, whilst aerosols generated from 2.5 microm liposomes were fractionated in the twin impinger with the largest liposomes collected in the upper stage.

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