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Article

Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process

1
Chemical Engineering Department, Loughborough University, Loughborough LE11 3TU, UK
2
Department of Physics, University of Jyväskylä, Jyväskylä FI-40014, Finland
3
School of Life Sciences and Warwick Integrative Synthetic Biology Centre, University of Warwick, Coventry CV4 7AL, UK
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2019, 11(9), 475; https://doi.org/10.3390/pharmaceutics11090475
Received: 16 July 2019 / Revised: 7 September 2019 / Accepted: 10 September 2019 / Published: 14 September 2019
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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. View Full-Text
Keywords: microencapsulation; bacteriophage therapy; controlled release; enteric infections; pH-triggered release; E. coli; Eudragit S100 microencapsulation; bacteriophage therapy; controlled release; enteric infections; pH-triggered release; E. coli; Eudragit S100
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MDPI and ACS Style

Vinner, G.K.; Richards, K.; Leppanen, M.; Sagona, A.P.; Malik, D.J. Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process. Pharmaceutics 2019, 11, 475. https://doi.org/10.3390/pharmaceutics11090475

AMA Style

Vinner GK, Richards K, Leppanen M, Sagona AP, Malik DJ. Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process. Pharmaceutics. 2019; 11(9):475. https://doi.org/10.3390/pharmaceutics11090475

Chicago/Turabian Style

Vinner, Gurinder K., Kerry Richards, Miika Leppanen, Antonia P. Sagona, and Danish J. Malik. 2019. "Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process" Pharmaceutics 11, no. 9: 475. https://doi.org/10.3390/pharmaceutics11090475

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