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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
Summary
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.
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