Microencapsulation of Salmonella-Specific Bacteriophage Felix O1 Using Spray-Drying in a pH-Responsive Formulation and Direct Compression Tableting of Powders into a Solid Oral Dosage Form
Vinner, G. K., Rezaie-Yazdi, Z., Leppänen, M., Stapley, A. G., Leaper, M. C., & Malik, D. J. (2019). Microencapsulation of Salmonella-Specific Bacteriophage Felix O1 Using Spray-Drying in a pH-Responsive Formulation and Direct Compression Tableting of Powders into a Solid Oral Dosage Form. Pharmaceuticals, 12(1), Article 43. https://doi.org/10.3390/ph12010043
Julkaistu sarjassa
PharmaceuticalsTekijät
Päivämäärä
2019Tekijänoikeudet
© 2019 by The Authors.
The treatment of enteric bacterial infections using oral bacteriophage therapy can be
challenging since the harsh acidic stomach environment renders phages inactive during transit
through the gastrointestinal tract. Solid oral dosage forms allowing site-specific gastrointestinal
delivery of high doses of phages, e.g., using a pH or enzymatic trigger, would be a game changer for
the nascent industry trying to demonstrate the efficacy of phages, including engineered phages for gut
microbiome modulation in expensive clinical trials. Spray-drying is a scalable, low-cost process for
producing pharmaceutical agents in dry powder form. Encapsulation of a model Salmonella-specific
phage (Myoviridae phage Felix O1) was carried out using the process of spray-drying, employing
a commercially available Eudragit S100® pH-responsive anionic copolymer composed of methyl
methacrylate-co-methacrylic acid formulated with trehalose. Formulation and processing conditions
were optimised to improve the survival of phages during spray-drying, and their subsequent
protection upon exposure to simulated gastric acidity was demonstrated. Addition of trehalose to the
formulation was shown to protect phages from elevated temperatures and desiccation encountered
during spray-drying. Direct compression of spray-dried encapsulated phages into tablets was shown
to significantly improve phage protection upon exposure to simulated gastric fluid. The results
reported here demonstrate the significant potential of spray-dried pH-responsive formulations for
oral delivery of bacteriophages targeting gastrointestinal applications.
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https://converis.jyu.fi/converis/portal/detail/Publication/28992352
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