Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process
A scalable low-shear membrane emulsification process was used to produce microencapsulated <i>Escherichia coli</i>-phages in a solid oral dosage form. Uniform pH-responsive composite microparticles (mean size ~100 µm) composed of Eudragit<sup>®</sup> S100 an...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2019-09-01
|
Series: | Pharmaceutics |
Subjects: | |
Online Access: | https://www.mdpi.com/1999-4923/11/9/475 |
Summary: | A scalable low-shear membrane emulsification process was used to produce microencapsulated <i>Escherichia coli</i>-phages in a solid oral dosage form. Uniform pH-responsive composite microparticles (mean size ~100 µm) composed of Eudragit<sup>®</sup> 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 <i>E. coli</i>. Encapsulated phages were also shown to be effective in killing actively growing <i>E. coli</i> 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. |
---|---|
ISSN: | 1999-4923 |