Prolongation of Fate of Bacteriophages In Vivo by Polylactic-Co-Glycolic-Acid/Alginate-Composite Encapsulation

Abstract

With concern growing over antibiotics resistance, the use of bacteriophages to combat resistant bacteria has been suggested as an alternative strategy with which to enable the selective control of targeted pathogens. One major challenge that restrains the therapeutic application of bacteriophages as antibacterial agents is their short lifespan, which limits their antibacterial effect in vivo. Here, we developed a polylactic-co-glycolic acid (PLGA)/alginate-composite microsphere for increasing the lifespan of bacteriophages in vivo. The alginate matrix in PLGA microspheres encapsulated the bacteriophages and protected them against destabilization by an organic solvent. Encapsulated bacteriophages were detected in the tissue for 28 days post-administration, while the bacteriophages administered without advanced encapsulation survived in vivo for only 3–5 days. The bacteriophages with extended fate showed prophylaxis against the bacterial pathogens for 28 days post-administration. This enhanced prophylaxis is presumed to have originated from the diminished immune response against these encapsulated bacteriophages because of their controlled release. Collectively, composite encapsulation has prophylactic potential against bacterial pathogens that threaten food safety and public health.

Optimizing the formulation of Erwinia bacteriophages for improved UV stability and adsorption on apple leaves

“…One of the critical factors that should be considered for applying phages as biocontrol agents is their fate on targeted environment [ 33 , 37 , 48 , 65 ]. The plant surface is characterized by its anti-adhesive nature, which makes it difficult for phages to adhere and to penetrate the plant tissues [ 66 ].…”

The Biotechnological Application of Bacteriophages: What to Do and Where to Go in the Middle of the Post-Antibiotic Era

“…Singla et al employed liposome encapsulation to shield phages from neutralization through phage-specific antibodies, leading to an increased protection effect in vivo [ 154 , 155 ]. Kim et al extended phage survival in vivo by encapsulating biocompatible substances, thereby mitigating the immune response to phages [ 156 ].…”

Application of Physical-Chemical Approaches for Encapsulation of Active Substances in Pharmaceutical and Food Industries

“…Double water-in-oil-in-water (W/O/W) emulsion was conducted by Kim, S. et al [62]. PLGA microspheres were prepared using a bacteriophage solution of pAh-6C in phosphate buffered saline (PBS), mixed with PLGA, and dissolved in dichloromethane to form a W/O emulsion.…”

“…Calcium chloride solution was added and homogenized to crosslink the alginate. To the emulsion was added deionized water and, after stirring and evaporating, microspheres were obtained [62].…”