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Microencapsulation of enteric bacteriophages in a pH-responsive solid oral dosage formulation using a scalable membrane emulsification process
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Vinner, Gurinder K., Richards, Kerry, Leppanen, Miika, Sagona, Antonia P. and Malik, Danish J. (2019) Microencapsulation of enteric bacteriophages in a pH-responsive solid oral dosage formulation using a scalable membrane emulsification process. Pharmaceutics, 11 (9). 475. doi:10.3390/pharmaceutics11090475 ISSN 1424-8247.
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Official URL: https://doi.org/10.3390/pharmaceutics11090475
Abstract
A scalable low-shear membrane emulsification process was used to produce microencapsulated Escherichia coli-phages in a solid oral dosage form. Uniform pH-responsive composite microparticles (mean size ~100 µm) composed of Eudragit® S100 and alginate were produced. The internal microstructure of the gelled microcapsules was studied using ion-milling and imaging, which showed that the microparticles had a solid internal core. The microencapsulation process significantly protected phages upon prolonged exposure to a simulated gastric acidic environment. Encapsulated phages that had been pre-exposed to simulated gastric acid were added to actively growing bacterial cells using in vitro cell cultures and were found to be effective in killing E. coli. Encapsulated phages were also shown to be effective in killing actively growing E. coli in the presence of human epithelial cells. Confocal microscopy images showed that the morphology of encapsulated phage-treated epithelial cells was considerably better than controls without phage treatment. The encapsulated phages were stable during refrigerated storage over a four-week period. The process of membrane emulsification is highly scalable and is a promising route to produce industrial quantities of pH-responsive oral solid dosage forms suitable for delivering high titres of viable phages to the gastrointestinal tract.
Item Type: | Journal Article | |||||||||
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Subjects: | Q Science > QR Microbiology R Medicine > RS Pharmacy and materia medica |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | |||||||||
Library of Congress Subject Headings (LCSH): | Drug resistance in microorganisms, Bacterial diseases -- Pathogenesis, Microencapsulation, Bacteriophages -- Therapeutic use, Intestines -- Infections, Escherichia coli | |||||||||
Journal or Publication Title: | Pharmaceutics | |||||||||
Publisher: | MDPI | |||||||||
ISSN: | 1424-8247 | |||||||||
Official Date: | 14 September 2019 | |||||||||
Dates: |
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Volume: | 11 | |||||||||
Number: | 9 | |||||||||
Article Number: | 475 | |||||||||
DOI: | 10.3390/pharmaceutics11090475 | |||||||||
Status: | Peer Reviewed | |||||||||
Publication Status: | Published | |||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||
Date of first compliant deposit: | 13 September 2019 | |||||||||
Date of first compliant Open Access: | 13 September 2019 | |||||||||
RIOXX Funder/Project Grant: |
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