Disturbance of Commensal Microbiota
It is crucial to know about and investigate all interactions of phages with human niche microbiota when using phages as therapeutic agents, and specifically any possible perturbations in the human microbiota due to strong selective pressure of lytic phages. Additional mechanistic investigations that clearly show the nature of host–phage dynamics in niche microbiota will help to hasten the process of obtaining regulatory approval for phage therapy in Western medicine.94 This is sometimes mentioned as a concern. However, phages are generally species specific, so that disturbance of the commensal microbiota is minimal.95
共生微生物群的干扰 在使用噬菌体作为治疗药物时，了解和研究噬菌体与人类生态位微生物群的所有相互作用至关重要，特别是噬菌体的强大选择压力可能对人类微生物群造成的任何干扰。进行更多的机理研究，清楚地显示宿主-噬菌体在生态位微生物群中的动态性质，将有助于加快噬菌体疗法在西方医学中获得监管部门批准的进程。 94 有时人们会把这一点作为一个担忧。不过，噬菌体通常具有物种特异性，因此对共生微生物群的干扰很小。 95
Quality and Safety Requirements
The safety and quality of phage preparations will determine the success of phage therapy. The production of phages for therapy must follow strict regulations to assure their quality for their intended use, even if no clear guidelines have been established for the manufacture of phages.96 The presence of impurities such as endotoxins must be avoided or kept below the threshold in phage preparations, but none has reached the optimal level so far. The quality of phage therapy is regulated by assessing and checking their stability, sterility, and cytotoxicity, and performing pH measurements regularly.97
质量和安全要求 噬菌体制剂的安全和质量将决定噬菌体疗法的成败。用于治疗的噬菌体的生产必须遵守严格的规定，以确保其质量符合预期用途，即使尚未制定明确的噬菌体生产准则。 96 必须避免噬菌体制剂中出现内毒素等杂质或将其含量控制在阈值以下，但迄今为止还没有一种噬菌体制剂达到最佳水平。通过评估和检查噬菌体的稳定性、无菌性和细胞毒性，并定期进行 pH 值测量，来规范噬菌体疗法的质量。 97
Phage Storage and Handling
Phages for therapy are mainly in the form of water suspension and are freshly made. There is not enough understanding of how to process phages with well-defined pharmaceutical properties and stability. Phages lack stability, which is one of the ideal characteristics of drugs, along with specificity, high affinity, solubility, and safety.98,99 They are partially stable in solution owing to their protein structure. The structural instability of phages makes long-term storage difficult and cooling is essential to store phage preparations. Phages in aqueous solution can be stabilized by the addition of stability enhancers or by processing them into another formulation, through lyophilization, spray drying, or incorporating them into ointments, biodegradable polymer matrices, or microparticles.100–102
噬菌体的储存和处理 用于治疗的噬菌体主要以水悬浮液的形式存在，并且是新鲜制成的。人们对如何处理具有明确药物特性和稳定性的噬菌体还缺乏足够的了解。噬菌体除了特异性、高亲和性、溶解性和安全性之外，还缺乏药物的理想特性之一–稳定性。由于噬菌体的蛋白质结构，它们在溶液中具有部分稳定性。噬菌体结构的不稳定性使其难以长期保存，因此冷却是保存噬菌体制剂的必要条件。水溶液中的噬菌体可通过添加稳定性增强剂或通过冻干、喷雾干燥或将其纳入软膏、生物可降解聚合物基质或微粒等方法加工成另一种制剂来加以稳定。 100–102