The Experts below are selected from a list of 282 Experts worldwide ranked by ideXlab platform
Dominic Sauvageau - One of the best experts on this subject based on the ideXlab platform.
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Anti-Tuberculosis BacterioPhage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler
Pharmaceutical Research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Zaritza Petrova, Dominic SauvageauAbstract:Purpose To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Methods Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log_10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis , were used to quantify Phage Titer . Results Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log_10(pfu/mL). Active Phage delivery rate was significantly greater ( p
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anti tuberculosis bacterioPhage d29 delivery with a vibrating mesh nebulizer jet nebulizer and soft mist inhaler
Pharmaceutical Research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Zaritza O Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Dominic SauvageauAbstract:To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify Phage Titer. Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active Phage delivery rate was significantly greater (p < 0.01) for the vibrating mesh nebulizer (3.3x108 ± 0.8x108 pfu/min) than for the jet nebulizer (5.4x104 ± 1.3x104 pfu/min). The soft mist inhaler delivered 4.6x106 ± 2.0x106 pfu per 11.6 ± 1.6 μL ex-actuator dose. Delivering active Phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing Phage D29 under the tested conditions, due to substantial Titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.
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Anti-Tuberculosis BacterioPhage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler.
Pharmaceutical research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Zaritza O Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Dominic SauvageauAbstract:To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify Phage Titer. Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active Phage delivery rate was significantly greater (p
Nicholas B Carrigy - One of the best experts on this subject based on the ideXlab platform.
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Development of a Lyophilization Process for Campylobacter BacterioPhage Storage and Transport.
Microorganisms, 2020Co-Authors: Lu Liang, Nicholas B Carrigy, Samuel Kariuki, Peter Muturi, Robert S. Onsare, Tobi E. Nagel, Reinhard Vehring, Phillippa L. Connerton, Ian F. ConnertonAbstract:BacterioPhages are a sustainable alternative to control pathogenic bacteria in the post-antibiotic era. Despite promising reports, there are still obstacles to Phage use, notably Titer stability and transport-associated expenses for applications in food and agriculture. In this study, we have developed a lyophilization approach to maintain Phage Titers, ensure efficacy and reduce transport costs of Campylobacter bacterioPhages. Lyophilization methods were adopted with various excipients to enhance stabilization in combination with packaging options for international transport. Lyophilization of Eucampyvirinae CP30A using tryptone formed a cake that limited processing Titer reduction to 0.35 ± 0.09 log10 PFU mL−1. Transmission electron microscopy revealed the initial Titer reduction was associated with capsid collapse of a subpopulation. Freeze-dried Phages were generally stable under refrigerated vacuum conditions and showed no significant Titer changes over 3 months incubation at 4 °C (p = 0.29). Reduced stability was observed for lyophilized Phages that were incubated either at 30 °C under vacuum or at 4 °C at 70% or 90% relative humidity. Refrigerated international transport and rehydration of the cake resulted in a total Phage Titer reduction of 0.81 ± 0.44 log10 PFU mL−1. A significantly higher Titer loss was observed for Phages that were not refrigerated during transport (2.03 ± 0.32 log10 PFU mL−1). We propose that lyophilization offers a convenient method to preserve and transport Campylobacter Phages, with minimal Titer reduction after the drying process.
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Anti-Tuberculosis BacterioPhage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler
Pharmaceutical Research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Zaritza Petrova, Dominic SauvageauAbstract:Purpose To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Methods Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log_10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis , were used to quantify Phage Titer . Results Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log_10(pfu/mL). Active Phage delivery rate was significantly greater ( p
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anti tuberculosis bacterioPhage d29 delivery with a vibrating mesh nebulizer jet nebulizer and soft mist inhaler
Pharmaceutical Research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Zaritza O Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Dominic SauvageauAbstract:To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify Phage Titer. Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active Phage delivery rate was significantly greater (p < 0.01) for the vibrating mesh nebulizer (3.3x108 ± 0.8x108 pfu/min) than for the jet nebulizer (5.4x104 ± 1.3x104 pfu/min). The soft mist inhaler delivered 4.6x106 ± 2.0x106 pfu per 11.6 ± 1.6 μL ex-actuator dose. Delivering active Phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing Phage D29 under the tested conditions, due to substantial Titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.
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Anti-Tuberculosis BacterioPhage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler.
Pharmaceutical research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Zaritza O Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Dominic SauvageauAbstract:To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify Phage Titer. Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active Phage delivery rate was significantly greater (p
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Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections
Pharmaceutical Research, 2016Co-Authors: Sharon S Y Leung, Nicholas B Carrigy, Warwick J Britton, Reinhard Vehring, Thaigarajan Parumasivam, Fiona G. Gao, Warren H. Finlay, Sandra Morales, Elizabeth Kutter, Hakkim ChanAbstract: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.
Hakkim Chan - One of the best experts on this subject based on the ideXlab platform.
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Anti-Tuberculosis BacterioPhage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler
Pharmaceutical Research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Zaritza Petrova, Dominic SauvageauAbstract:Purpose To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Methods Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log_10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis , were used to quantify Phage Titer . Results Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log_10(pfu/mL). Active Phage delivery rate was significantly greater ( p
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anti tuberculosis bacterioPhage d29 delivery with a vibrating mesh nebulizer jet nebulizer and soft mist inhaler
Pharmaceutical Research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Zaritza O Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Dominic SauvageauAbstract:To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify Phage Titer. Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active Phage delivery rate was significantly greater (p < 0.01) for the vibrating mesh nebulizer (3.3x108 ± 0.8x108 pfu/min) than for the jet nebulizer (5.4x104 ± 1.3x104 pfu/min). The soft mist inhaler delivered 4.6x106 ± 2.0x106 pfu per 11.6 ± 1.6 μL ex-actuator dose. Delivering active Phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing Phage D29 under the tested conditions, due to substantial Titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.
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Anti-Tuberculosis BacterioPhage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler.
Pharmaceutical research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Zaritza O Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Dominic SauvageauAbstract:To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify Phage Titer. Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active Phage delivery rate was significantly greater (p
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Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections
Pharmaceutical Research, 2016Co-Authors: Sharon S Y Leung, Nicholas B Carrigy, Warwick J Britton, Reinhard Vehring, Thaigarajan Parumasivam, Fiona G. Gao, Warren H. Finlay, Sandra Morales, Elizabeth Kutter, Hakkim ChanAbstract: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.
Sharon S Y Leung - One of the best experts on this subject based on the ideXlab platform.
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Anti-Tuberculosis BacterioPhage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler
Pharmaceutical Research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Zaritza Petrova, Dominic SauvageauAbstract:Purpose To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Methods Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log_10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis , were used to quantify Phage Titer . Results Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log_10(pfu/mL). Active Phage delivery rate was significantly greater ( p
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anti tuberculosis bacterioPhage d29 delivery with a vibrating mesh nebulizer jet nebulizer and soft mist inhaler
Pharmaceutical Research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Zaritza O Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Dominic SauvageauAbstract:To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify Phage Titer. Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active Phage delivery rate was significantly greater (p < 0.01) for the vibrating mesh nebulizer (3.3x108 ± 0.8x108 pfu/min) than for the jet nebulizer (5.4x104 ± 1.3x104 pfu/min). The soft mist inhaler delivered 4.6x106 ± 2.0x106 pfu per 11.6 ± 1.6 μL ex-actuator dose. Delivering active Phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing Phage D29 under the tested conditions, due to substantial Titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.
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Anti-Tuberculosis BacterioPhage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler.
Pharmaceutical research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Zaritza O Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Dominic SauvageauAbstract:To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify Phage Titer. Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active Phage delivery rate was significantly greater (p
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Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections
Pharmaceutical Research, 2016Co-Authors: Sharon S Y Leung, Nicholas B Carrigy, Warwick J Britton, Reinhard Vehring, Thaigarajan Parumasivam, Fiona G. Gao, Warren H. Finlay, Sandra Morales, Elizabeth Kutter, Hakkim ChanAbstract: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.
Warwick J Britton - One of the best experts on this subject based on the ideXlab platform.
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Anti-Tuberculosis BacterioPhage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler
Pharmaceutical Research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Zaritza Petrova, Dominic SauvageauAbstract:Purpose To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Methods Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log_10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis , were used to quantify Phage Titer . Results Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log_10(pfu/mL). Active Phage delivery rate was significantly greater ( p
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anti tuberculosis bacterioPhage d29 delivery with a vibrating mesh nebulizer jet nebulizer and soft mist inhaler
Pharmaceutical Research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Zaritza O Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Dominic SauvageauAbstract:To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify Phage Titer. Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active Phage delivery rate was significantly greater (p < 0.01) for the vibrating mesh nebulizer (3.3x108 ± 0.8x108 pfu/min) than for the jet nebulizer (5.4x104 ± 1.3x104 pfu/min). The soft mist inhaler delivered 4.6x106 ± 2.0x106 pfu per 11.6 ± 1.6 μL ex-actuator dose. Delivering active Phage requires a prudent choice of inhalation device. The jet nebulizer was not a good choice for aerosolizing Phage D29 under the tested conditions, due to substantial Titer reduction likely occurring during droplet production. The vibrating mesh nebulizer is recommended for animal inhalation studies requiring large amounts of D29 aerosol, whereas the soft mist inhaler may be useful for self-administration of D29 aerosol.
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Anti-Tuberculosis BacterioPhage D29 Delivery with a Vibrating Mesh Nebulizer, Jet Nebulizer, and Soft Mist Inhaler.
Pharmaceutical research, 2017Co-Authors: Nicholas B Carrigy, Rachel Yoon Kyung Chang, Sharon S Y Leung, Melissa Harrison, Zaritza O Petrova, Welkin H Pope, Graham F Hatfull, Warwick J Britton, Hakkim Chan, Dominic SauvageauAbstract:To compare Titer reduction and delivery rate of active anti-tuberculosis bacterioPhage (Phage) D29 with three inhalation devices. Phage D29 lysate was amplified to a Titer of 11.8 ± 0.3 log10(pfu/mL) and diluted 1:100 in isotonic saline. Filters captured the aerosolized saline D29 preparation emitted from three types of inhalation devices: 1) vibrating mesh nebulizer; 2) jet nebulizer; 3) soft mist inhaler. Full-plate plaque assays, performed in triplicate at multiple dilution levels with the surrogate host Mycobacterium smegmatis, were used to quantify Phage Titer. Respective Titer reductions for the vibrating mesh nebulizer, jet nebulizer, and soft mist inhaler were 0.4 ± 0.1, 3.7 ± 0.1, and 0.6 ± 0.3 log10(pfu/mL). Active Phage delivery rate was significantly greater (p
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Production of Inhalation Phage Powders Using Spray Freeze Drying and Spray Drying Techniques for Treatment of Respiratory Infections
Pharmaceutical Research, 2016Co-Authors: Sharon S Y Leung, Nicholas B Carrigy, Warwick J Britton, Reinhard Vehring, Thaigarajan Parumasivam, Fiona G. Gao, Warren H. Finlay, Sandra Morales, Elizabeth Kutter, Hakkim ChanAbstract: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.