The Pathways to Create Containers for Bacteriophage Delivery

Abstract

Antimicrobial resistance is a global public health threat. One of the possible ways to solve this problem is phage therapy, but the instability of bacteriophages hinders the development of this approach. A bacteriophage delivery system that stabilizes the phage is one of the possible solutions to this problem. This study is dedicated to exploring methods to create encapsulated forms of bacteriophages for delivery. We studied the effect of proteolytic enzymes on the destruction of the polyelectrolyte microcapsule shell and revealed that protease from Streptomyces griseus was able to destroy the membrane of the microcapsule (dextran sulfate/polyarginine)3 ((DS/PArg)3). In addition, the protease decreased the activity of the bacteriophage in the second hour of incubation, and the phage lost activity after 16 h. It was found that a medium with pH 9.02 did not affect the survival of the bacteriophage or E. coli. The bacteriophages were encapsulated into polyelectrolyte microcapsules (DS/PArg)3. It was established that it is impossible to use microcapsules as a means of delivering bacteriophages since the bacteriophages are inactivated. When bacteriophages were included inside a CaCO3 core, it was demonstrated that the phage retained activity before and after the dissolution of the CaCO3 particle. From the results of this study, we recommend using CaCO3 microparticles as a container for bacteriophage delivery through the acidic stomach barrier.

Phage Delivery Strategies for Biocontrolling Human, Animal, and Plant Bacterial Infections: State of the Art

“…Among inorganic particles, porous calcium phosphate particles are most often used as carriers for phage virions [ 73 ]. Carbohydrate biopolymers used as matrices for microencapsulation should be non-toxic and biodegradable, capable of forming gels.…”

“…Chitosan is the second most used organic polymer for bacteriophage encapsulation and delivery. Other polymer compounds used to create microcapsules are also cited in the literature, such as poly(ethylene oxide)/cellulose diacetate fibers, poly(acryl starch), and poly(lactide-co-glycolide) [ 73 ]. Synthetic polymers (such as Eudragit ® ) in association with natural polymers [ 76 ] or alone [ 67 ] have also been used for phage encapsulation.…”

“…Salmonella enterica, Shigella flexneri and Escherichia coli Sodium tripolyphosphate; gelation; acetic acid and chitosan [72] Escherichia coli Sodium alginate and low methoxylated (LM) pectin (33% esterification degree) [74] Escherichia coli Sodium alginate and chitosan-acetate buffer solution [81] Escherichia coli Sodium alginate and chitosan, polyethylene imine (PEI) [82] Proteus vulgaris and Escherichia coli Na 2 CO 3 and CaCl 2 (microspherolits) with alternate adsorption of oppositely charged polyelectrolytes (polyelectrolyte microcapsules) [73] Escherichia coli Chitosan-alginate coating shell [83] Another way to stabilize the phage particles and extend their persistence at the site of infection while allowing access to the inside of eukaryotic cells is by encapsulating the phage virions within the aqueous core of liposomes [53]. Bacteriophage virions cannot diffuse across cellular membranes, which would be a prerequisite for them to reach, infect, and lyse intracellular bacterial pathogens.…”