Formulation, stabilisation and encapsulation of bacteriophage for phage therapy

作者：Danish J. Malik, I. J. Sokolov, Gurinder K. Vinner, Francesco M. Mancuso, Salvatore Cinquerrui, Goran T. Vladisavljević, Martha R. J. Clokie, Natalie J. Garton, A.G.F. Stapley, Anna Kirpichnikova · 发表于：Advances in Colloid and Interface Science · 年份：2017 · DOI：10.1016/j.cis.2017.05.014 · 被引用次数：590 · 研究领域：Bacteriophages and microbial interactions、Monoclonal and Polyclonal Antibodies Research、Microbial infections and disease research

Against a backdrop of global antibiotic resistance and increasing awareness of the importance of the human microbiota, there has been resurgent interest in the potential use of bacteriophages for therapeutic purposes, known as phage therapy. A number of phage therapy phase I and II clinical trials have concluded, and shown phages don't present significant adverse safety concerns. These clinical trials used simple phage suspensions without any formulation and phage stability was of secondary concern. Phages have a limited stability in solution, and undergo a significant drop in phage titre during processing and storage which is unacceptable if phages are to become regulated pharmaceuticals, where stable dosage and well defined pharmacokinetics and pharmacodynamics are de rigueur. Animal studies have shown that the efficacy of phage therapy outcomes depend on the phage concentration (i.e. the dose) delivered at the site of infection, and their ability to target and kill bacteria, arresting bacterial growth and clearing the infection. In addition, in vitro and animal studies have shown the importance of using phage cocktails rather than single phage preparations to achieve better therapy outcomes. The in vivo reduction of phage concentration due to interactions with host antibodies or other clearance mechanisms may necessitate repeated dosing of phages, or sustained release approaches. Modelling of phage-bacterium population dynamics reinforces these points. Surprisingly little ...