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Microencapsulation of salmonella-specific bacteriophage Felix O1 using spray-drying in a pH-responsive formulation and direct compression tableting of powders into a solid oral dosage form

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posted on 09.04.2019, 13:16 by Gurinder K. Vinner, Zahra Rezaie-Yazdi, Miika Leppanen, Andy Stapley, Mark Leaper, Danish Malik
The treatment of enteric bacterial infections using oral bacteriophage therapy can be challenging since the harsh acidic stomach environment renders phages inactive during transit through the gastrointestinal tract. Solid oral dosage forms allowing site-specific gastrointestinal delivery of high doses of phages, e.g., using a pH or enzymatic trigger, would be a game changer for the nascent industry trying to demonstrate the efficacy of phages, including engineered phages for gut microbiome modulation in expensive clinical trials. Spray-drying is a scalable, low-cost process for producing pharmaceutical agents in dry powder form. Encapsulation of a model Salmonella-specific phage (Myoviridae phage Felix O1) was carried out using the process of spray-drying, employing a commercially available Eudragit S100® pH-responsive anionic copolymer composed of methyl methacrylate-co-methacrylic acid formulated with trehalose. Formulation and processing conditions were optimised to improve the survival of phages during spray-drying, and their subsequent protection upon exposure to simulated gastric acidity was demonstrated. Addition of trehalose to the formulation was shown to protect phages from elevated temperatures and desiccation encountered during spray-drying. Direct compression of spray-dried encapsulated phages into tablets was shown to significantly improve phage protection upon exposure to simulated gastric fluid. The results reported here demonstrate the significant potential of spray-dried pH-responsive formulations for oral delivery of bacteriophages targeting gastrointestinal applications.

Funding

This research was funded by the UK Engineering and Physical Sciences Research Council (EPSRC), grant number EP/M027341/1 and the APC was funded by EPSRC.

History

School

  • Aeronautical, Automotive, Chemical and Materials Engineering

Department

  • Chemical Engineering

Published in

Pharmaceuticals (Basel)

Volume

12

Issue

1

Citation

VINNER, G.K. ... et al, 2019. Microencapsulation of salmonella-specific bacteriophage Felix O1 using spray-drying in a pH-responsive formulation and direct compression tableting of powders into a solid oral dosage form. Pharmaceuticals, 12 (1), 43.

Publisher

MDPI (© The Authors)

Version

VoR (Version of Record)

Publisher statement

This work is made available according to the conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/ by/4.0/

Acceptance date

18/03/2019

Publication date

2019-03-22

Notes

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

ISSN

1424-8247

Other identifier

ph12010043

Language

en

Location

Switzerland

Licence

Exports