Nicholas B Carrigy1, Rachel Y Chang2, Sharon S Y Leung2, Melissa Harrison3, Zaritza Petrova4, Welkin H Pope4, Graham F Hatfull4, Warwick J Britton5, Hak-Kim Chan2, Dominic Sauvageau3, Warren H Finlay1, Reinhard Vehring6,7. 1. Department of Mechanical Engineering, University of Alberta, Edmonton, AB, Canada. 2. Advanced Drug Delivery Group, Faculty of Pharmacy, University of Sydney, Sydney, Australia. 3. Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada. 4. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA. 5. Centenary Institute of Cancer Medicine and Cell Biology, and Sydney Medical School, University of Sydney, Sydney, Australia. 6. Department of Mechanical Engineering, University of Alberta, Edmonton, AB, Canada. reinhard.vehring@ualberta.ca. 7. Department of Mechanical Engineering, 10-203 Donadeo Innovation Centre for Engineering, University of Alberta, 9211 116th Street NW, Edmonton, AB, T6G 1H9, Canada. reinhard.vehring@ualberta.ca.
Abstract
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 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. 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 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. CONCLUSIONS: 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.
PURPOSE: To compare titer reduction and delivery rate of active anti-tuberculosisbacteriophage (phage) D29 with three inhalation devices. METHODS: 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. 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 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. CONCLUSIONS: 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.
Authors: Eugene R Arulmuthu; David J Williams; Helen Baldascini; Henk K Versteeg; Mike Hoare Journal: Biotechnol Bioeng Date: 2007-12-01 Impact factor: 4.530
Authors: Susan Hoe; Mohammed A Boraey; James W Ivey; Warren H Finlay; Reinhard Vehring Journal: J Aerosol Med Pulm Drug Deliv Date: 2013-12-03 Impact factor: 2.849
Authors: Elizabeth Kutter; Daniel De Vos; Guram Gvasalia; Zemphira Alavidze; Lasha Gogokhia; Sarah Kuhl; Stephen T Abedon Journal: Curr Pharm Biotechnol Date: 2010-01 Impact factor: 2.837
Authors: Sharon S Y Leung; Thaigarajan Parumasivam; Fiona G Gao; Nicholas B Carrigy; Reinhard Vehring; Warren H Finlay; Sandra Morales; Warwick J Britton; Elizabeth Kutter; Hak-Kim Chan Journal: Pharm Res Date: 2016-02-29 Impact factor: 4.200
Authors: Rebekah M Dedrick; Krista G Freeman; Jan A Nguyen; Asli Bahadirli-Talbott; Mitchell E Cardin; Madison Cristinziano; Bailey E Smith; Soowan Jeong; Elisa H Ignatius; Cheng Ting Lin; Keira A Cohen; Graham F Hatfull Journal: Open Forum Infect Dis Date: 2022-04-12 Impact factor: 4.423
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
Authors: Nicholas B Carrigy; Sasha E Larsen; Valerie Reese; Tiffany Pecor; Melissa Harrison; Philip J Kuehl; Graham F Hatfull; Dominic Sauvageau; Susan L Baldwin; Warren H Finlay; Rhea N Coler; Reinhard Vehring Journal: Antimicrob Agents Chemother Date: 2019-09-16 Impact factor: 5.191
Authors: Hans Duyvejonck; Maya Merabishvili; Mario Vaneechoutte; Steven de Soir; Rosanna Wright; Ville-Petri Friman; Gilbert Verbeken; Daniel De Vos; Jean-Paul Pirnay; Els Van Mechelen; Stefan J T Vermeulen Journal: Viruses Date: 2021-05-08 Impact factor: 5.048