Sharon S Y Leung1, Thaigarajan Parumasivam1, Fiona G Gao1, Nicholas B Carrigy2, Reinhard Vehring2, Warren H Finlay2, Sandra Morales3, Warwick J Britton4, Elizabeth Kutter5, Hak-Kim Chan6. 1. Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia. 2. Department of Mechanical Engineering, University of Alberta, Edmonton, Alberta, T6G 2G8, Canada. 3. AmpliPhi Biosciences AU, 7/27 Dale Street, Brookvale, Sydney, NSW, 2100, Australia. 4. Tuberculosis Research Program, Centenary Institute and Sydney Medical School, University of Sydney, Sydney, NSW, 2006, Australia. 5. The Evergreen State College, Olympia, Washington, 98502, USA. 6. Faculty of Pharmacy, University of Sydney, Sydney, NSW, 2006, Australia. kim.chan@sydney.edu.au.
Abstract
PURPOSE: The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders. METHOD: A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1 = 60:20:20 and F2 = 40:40:20). The phage titer loss after the SFD and SD processes and in vitro aerosol performance of the produced powders were assessed. RESULTS: A significant titer loss (~2 log) was noted for droplet generation using an ultrasonic nozzle employed in the SFD method, but the conventional two-fluid nozzle used in the SD method was less destructive for the phage (~0.75 log loss). The phage were more vulnerable during the evaporative drying process (~0.75 log further loss) compared with the freeze drying step, which caused negligible phage loss. In vitro aerosol performance showed that the SFD powders (~80% phage recovery) provided better phage protection than the SD powders (~20% phage recovery) during the aerosolization process. Despite this, higher total lung doses were obtained for the SD formulations (SD-F1 = 13.1 ± 1.7 × 10(4) pfu and SD-F2 = 11.0 ± 1.4 × 10(4) pfu) than from their counterpart SFD formulations (SFD-F1 = 8.3 ± 1.8 × 10(4) pfu and SFD-F2 = 2.1 ± 0.3 × 10(4) pfu). CONCLUSION: Overall, the SD method caused less phage reduction during the powder formation process and the resulted powders achieved better aerosol performance for PEV2.
PURPOSE: The potential of aerosol phage therapy for treating lung infections has been demonstrated in animal models and clinical studies. This work compared the performance of two dry powder formation techniques, spray freeze drying (SFD) and spray drying (SD), in producing inhalable phage powders. METHOD: A Pseudomonas podoviridae phage, PEV2, was incorporated into multi-component formulation systems consisting of trehalose, mannitol and L-leucine (F1 = 60:20:20 and F2 = 40:40:20). The phage titer loss after the SFD and SD processes and in vitro aerosol performance of the produced powders were assessed. RESULTS: A significant titer loss (~2 log) was noted for droplet generation using an ultrasonic nozzle employed in the SFD method, but the conventional two-fluid nozzle used in the SD method was less destructive for the phage (~0.75 log loss). The phage were more vulnerable during the evaporative drying process (~0.75 log further loss) compared with the freeze drying step, which caused negligible phage loss. In vitro aerosol performance showed that the SFD powders (~80% phage recovery) provided better phage protection than the SD powders (~20% phage recovery) during the aerosolization process. Despite this, higher total lung doses were obtained for the SD formulations (SD-F1 = 13.1 ± 1.7 × 10(4) pfu and SD-F2 = 11.0 ± 1.4 × 10(4) pfu) than from their counterpart SFD formulations (SFD-F1 = 8.3 ± 1.8 × 10(4) pfu and SFD-F2 = 2.1 ± 0.3 × 10(4) pfu). CONCLUSION: Overall, the SD method caused less phage reduction during the powder formation process and the resulted powders achieved better aerosol performance for PEV2.
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Authors: Sharon S Y Leung; Thaigarajan Parumasivam; Fiona G Gao; Elizabeth A Carter; Nicholas B Carrigy; Reinhard Vehring; Warren H Finlay; Sandra Morales; Warwick J Britton; Elizabeth Kutter; Hak-Kim Chan Journal: Int J Pharm Date: 2017-02-03 Impact factor: 5.875
Authors: Sharon S Y Leung; Thaigarajan Parumasivam; An Nguyen; Thomas Gengenbach; Elizabeth A Carter; Nicholas B Carrigy; Hui Wang; Reinhard Vehring; Warren H Finlay; Sandra Morales; Warwick J Britton; Elizabeth Kutter; Hak-Kim Chan Journal: Eur J Pharm Biopharm Date: 2018-02-24 Impact factor: 5.571