Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process
A scalable low-shear membrane emulsification process was used to produce microencapsulated <i>Escherichia coli</i>-phages in a solid oral dosage form. Uniform pH-responsive composite microparticles (mean size ~100 µm) composed of Eudragit<sup>®</sup> S100 an...
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MDPI AG
2019-09-01
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Series: | Pharmaceutics |
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Online Access: | https://www.mdpi.com/1999-4923/11/9/475 |
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author | Gurinder K. Vinner Kerry Richards Miika Leppanen Antonia P. Sagona Danish J. Malik |
author_facet | Gurinder K. Vinner Kerry Richards Miika Leppanen Antonia P. Sagona Danish J. Malik |
author_sort | Gurinder K. Vinner |
collection | DOAJ |
description | A scalable low-shear membrane emulsification process was used to produce microencapsulated <i>Escherichia coli</i>-phages in a solid oral dosage form. Uniform pH-responsive composite microparticles (mean size ~100 µm) composed of Eudragit<sup>®</sup> 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 <i>E. coli</i>. Encapsulated phages were also shown to be effective in killing actively growing <i>E. coli</i> 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. |
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format | Article |
id | doaj.art-2c09e66268b6409993ae7840ca702d73 |
institution | Directory Open Access Journal |
issn | 1999-4923 |
language | English |
last_indexed | 2024-04-11T21:47:32Z |
publishDate | 2019-09-01 |
publisher | MDPI AG |
record_format | Article |
series | Pharmaceutics |
spelling | doaj.art-2c09e66268b6409993ae7840ca702d732022-12-22T04:01:21ZengMDPI AGPharmaceutics1999-49232019-09-0111947510.3390/pharmaceutics11090475pharmaceutics11090475Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification ProcessGurinder K. Vinner0Kerry Richards1Miika Leppanen2Antonia P. Sagona3Danish J. Malik4Chemical Engineering Department, Loughborough University, Loughborough LE11 3TU, UKChemical Engineering Department, Loughborough University, Loughborough LE11 3TU, UKDepartment of Physics, University of Jyväskylä, Jyväskylä FI-40014, FinlandSchool of Life Sciences and Warwick Integrative Synthetic Biology Centre, University of Warwick, Coventry CV4 7AL, UKChemical Engineering Department, Loughborough University, Loughborough LE11 3TU, UKA scalable low-shear membrane emulsification process was used to produce microencapsulated <i>Escherichia coli</i>-phages in a solid oral dosage form. Uniform pH-responsive composite microparticles (mean size ~100 µm) composed of Eudragit<sup>®</sup> 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 <i>E. coli</i>. Encapsulated phages were also shown to be effective in killing actively growing <i>E. coli</i> 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.https://www.mdpi.com/1999-4923/11/9/475microencapsulationbacteriophage therapycontrolled releaseenteric infectionspH-triggered release<i>E. coli</i>Eudragit S100 |
spellingShingle | Gurinder K. Vinner Kerry Richards Miika Leppanen Antonia P. Sagona Danish J. Malik Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process Pharmaceutics microencapsulation bacteriophage therapy controlled release enteric infections pH-triggered release <i>E. coli</i> Eudragit S100 |
title | Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process |
title_full | Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process |
title_fullStr | Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process |
title_full_unstemmed | Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process |
title_short | Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process |
title_sort | microencapsulation of enteric bacteriophages in a ph responsive solid oral dosage formulation using a scalable membrane emulsification process |
topic | microencapsulation bacteriophage therapy controlled release enteric infections pH-triggered release <i>E. coli</i> Eudragit S100 |
url | https://www.mdpi.com/1999-4923/11/9/475 |
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