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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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journal contribution
posted on 17.09.2019, 12:41 authored by Gurinder K. Vinner, Kerry Richards, Miika Leppanen, Antonia P. Sagona, Danish MalikDanish Malik
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.

Funding

EPSRC Grant no. EP/M027341/1, Tackling Antimicrobial Resistance: An Interdisciplinary Approach.

BBSRC Future Leader Fellowship (Grant no. BB/N011872/1)

History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

Pharmaceutics

Volume

11

Issue

9

Publisher

MDPI AG

Version

VoR (Version of Record)

Rights holder

© the Authors

Publisher statement

This is an Open Access Article. It is published by MDPI under the Creative Commons Attribution 4.0 Unported Licence (CC BY). Full details of this licence are available at: http://creativecommons.org/licenses/by/4.0/

Acceptance date

10/09/2019

Publication date

2019-09-14

Copyright date

2019

eISSN

1999-4923

Language

en

Depositor

Dr Danish Malik

Article number

475