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Published on: March 30, 2017
Feasibility of spray drying bacteriophages into respirable powders to combat pulmonary bacterial infections
Dieter Vandenheuvel1, Abhishek Singh, Katrien Vandersteegen
1Division of Gene Technology, Katholieke Universiteit Leuven, Heverlee, Belgium.
Abstract:
The use of bacterial viruses for antibacterial treatment (bacteriophage therapy) is currently being reevaluated. In this study, we analyze the potential of processing bacteriophages in a dry powder formulation, using a laboratory spray dryer. The phages were dried in the presence of lactose, trehalose or dextran 35, serving as an excipient to give the resulting powder the necessary bulk mass and offer protection to the delicate phage structure. Out of the three excipients tested, trehalose was found to be the most efficient in protecting the phages from temperature and shear stress throughout the spray drying process. A low inlet air temperature and atomizing force appeared to be the best parameter conditions for phage survival. Pseudomonas podovirus LUZ19 was remarkably stable, suffering less than 1 logarithmic unit reduction in phage titer. The phage titer of Staphyloccus phage Romulus-containing powders, a member of the Myoviridae family, showed more than 2.5 logarithmic units reduction. On the other hand, Romulus-containing powders showed more favorable characteristics for pulmonary delivery, with a high percentage of dry powder particles in the pulmonary deposition fraction (1-5 μm particle diameter). Even though the parameters were not optimized for spray drying all phages, it was demonstrated that spray drying phages with this industrial relevant and scalable set up was possible. The resulting powders had desirable size ranges for pulmonary delivery of phages with dry powder inhalers (DPIs).
Insights
Spray drying enables bacteriophage therapy by creating stable dry powders. Trehalose proved effective, yielding powders suitable for pulmonary delivery via dry powder inhalers (DPIs).
Area of Science:
- Microbiology
- Pharmaceutical Technology
- Biotechnology
Background:
- Bacteriophage therapy is being reevaluated as an alternative to antibiotics.
- Developing stable, administrable phage formulations is crucial for clinical application.
Purpose of the Study:
- To investigate the feasibility of spray drying bacteriophages into a dry powder formulation.
- To evaluate the protective effects of different excipients during spray drying.
- To assess the suitability of the resulting phage powders for pulmonary delivery.
Main Methods:
- Laboratory-scale spray drying of bacteriophages (Pseudomonas podovirus LUZ19 and Staphylococcus phage Romulus) using lactose, trehalose, or dextran 35 as excipients.
- Analysis of phage survival rates under different spray drying conditions (inlet air temperature, atomizing force).
- Characterization of powder particle size distribution for pulmonary deposition.
Main Results:
- Trehalose was the most effective excipient for protecting phages during spray drying.
- Lower inlet air temperatures and atomizing forces improved phage survival.
- Pseudomonas podovirus LUZ19 showed high stability (<1 log unit reduction), while Staphylococcus phage Romulus had a greater reduction (>2.5 log units).
- Romulus-containing powders exhibited favorable particle size characteristics (1-5 μm) for pulmonary delivery.
Conclusions:
- Spray drying is a viable and scalable method for producing bacteriophage dry powders.
- The formulation and process parameters significantly impact phage viability and powder characteristics.
- The resulting phage powders demonstrate potential for pulmonary delivery using dry powder inhalers (DPIs).
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