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The speed of development of resistance has been faster than the rate of discovery (Kelly et al., 2016). In the period between 19, 20 new classes of antibiotics were introduced to the market however, since 1962, there has been a discovery void with only two new classes reaching this stage (Coates et al., 2011). In much of the world outside Europe and North America, lifesaving antibiotics are sold without a prescription or oversight by health professionals (Laxminarayan et al., 2013). The problem of antibiotic resistance is a complex one requiring global coordination for antibiotic stewardship to preserve the efficacy of current treatments. The widespread inappropriate use of antibiotics in both humans (clinical medicine) and animals (livestock industry) worldwide has led to an acceleration in the emergence and global spread of multidrug antibiotic resistant bacterial clones (Morgan et al., 2011). Externally bound phages would be inactivated in the stomach acid resulting in low doses of phages delivered at the site of infection further downstream in the gastrointestinal tract. This overestimation may affect the efficacy of phage dose delivered at the site of infection. Previous published studies on phage encapsulation in liposomes may have overestimated the yield of encapsulated tailed phages.
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aureus K phages whilst retaining the activity of the encapsulated phages in order to estimate the yield of microfluidic encapsulation of large tailed phages. We were able to inactivate the liposome bound S. aureus phage K was found to interact with the liposome lipid bilayer resulting in large numbers of phages bound to the outside of the formed liposomes instead of being trapped inside them. coli T3 phages was affected by aggregation of T3 phages. The yield of encapsulated T3 phages was 10 9 PFU/ml and for phage K was much lower at 10 5 PFU/ml. Encapsulation of two model phages was undertaken, an Escherichia coli T3 podovirus (size ~65 nm) and a myovirus Staphylococcus aureus phage K (capsid head ~80 nm and phage tail length ~200 nm). In the present study we have evaluated the use of a microfluidic based technique for the encapsulation of bacteriophages in liposomes having mean sizes between 100 and 300 nm.
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Orally delivered phages tend to have short residence times in the gastrointestinal tract due to clinical symptoms such as diarrhea this may be addressed through mucoadhesion of liposomes. Additionally, liposome encapsulated phages may adhere to and diffuse within mucosa harboring resistant bacteria which are challenges in treating respiratory and gastrointestinal infections. A “Trojan Horse” approach utilizing liposome encapsulated phages may facilitate access to phagocytic cells infected with intracellular pathogens residing therein, e.g., to treat infections caused by Mycobacterium tuberculosis, Listeria, Salmonella, and Staphylococcus sp. Increasing antibiotic resistance in pathogenic microorganisms has led to renewed interest in bacteriophage therapy in both humans and animals.