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

Gurinder K Vinner1, Kerry Richards2, Miika Leppanen3

  • 1Chemical Engineering Department, Loughborough University, Loughborough, LE11 3TU, UK. G.Vinner@lboro.ac.uk.

Pharmaceutics
|September 22, 2019
PubMed

Insights

This study developed a scalable method to microencapsulate Escherichia coli-phages in pH-responsive oral dosage forms. The microencapsulated phages effectively killed E. coli bacteria and protected epithelial cells.

Area of Science:

  • Biotechnology
  • Materials Science
  • Microbiology

Background:

  • Bacteriophages (phages) offer a targeted alternative to antibiotics for treating bacterial infections.
  • Developing stable, orally deliverable phage formulations is crucial for gastrointestinal applications.
  • Existing methods for phage encapsulation often lack scalability or pH-responsiveness.

Purpose of the Study:

  • To develop a scalable membrane emulsification process for producing pH-responsive microencapsulated phages.
  • To evaluate the protective effect of microencapsulation against simulated gastric conditions.
  • To assess the efficacy of encapsulated phages against Escherichia coli in vitro and their impact on human epithelial cells.

Main Methods:

  • Utilized a low-shear membrane emulsification technique to create Eudragit S100 and alginate composite microparticles.
  • Investigated microparticle microstructure using ion-milling and imaging.
  • Assessed phage viability and efficacy against E. coli in simulated gastric conditions and co-culture models with human epithelial cells.
  • Evaluated stability during refrigerated storage.

Main Results:

  • Produced uniform, pH-responsive microparticles (~100 µm) with a solid internal core.
  • Microencapsulation significantly protected phages from simulated gastric acid.
  • Encapsulated phages demonstrated potent killing of E. coli in vitro, even in the presence of epithelial cells.
  • Phage treatment improved the morphology of epithelial cells compared to controls.
  • Encapsulated phages remained stable for four weeks under refrigeration.

Conclusions:

  • The scalable membrane emulsification process is suitable for industrial production of phage oral dosage forms.
  • pH-responsive microencapsulation effectively protects phages for targeted delivery to the gastrointestinal tract.
  • This approach shows promise for developing effective phage-based therapies against E. coli infections.
Keywords:
E. coliEudragit S100bacteriophage therapycontrolled releaseenteric infectionsmicroencapsulationpH-triggered release

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