A1 Journal article (refereed)
Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process (2019)

Vinner, G. K., Richards, K., Leppänen, M., Sagona, A. P., & Malik 1, D. J. (2019). Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process. Pharmaceutics, 11(9), Article 475. https://doi.org/10.3390/pharmaceutics11090475

JYU authors or editors

Publication details

All authors or editors: Vinner, Gurinder K.; Richards, Kerry; Leppänen, Miika; Sagona, Antonia P.; Malik 1, Danish J.

Journal or series: Pharmaceutics

eISSN: 1999-4923

Publication year: 2019

Volume: 11

Issue number: 9

Article number: 475

Publisher: MDPI

Publication country: Switzerland

Publication language: English

DOI: https://doi.org/10.3390/pharmaceutics11090475

Publication open access: Openly available

Publication channel open access: Open Access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/65677

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.

Keywords: bacteriophages; phage therapy; Enterobacteriaceae; gastroenteritis; drug design; microstructures; foils (films)

Free keywords: microencapsulation; bacteriophage therapy; controlled release; enteric infections; pH-triggered release; E. coli; Eudragit S100

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2019

JUFO rating: 1