Supplementary Information Files for "Microencapsulation of Salmonella-Specific Bacteriophage Felix O1 Using Spray-Drying in a pH-Responsive Formulation and Direct Compression Tableting of Powders into a Solid Oral Dosage Form"

Supplementary Information Files for "Microencapsulation of Salmonella-Specific Bacteriophage Felix O1 Using Spray-Drying in a pH-Responsive Formulation and Direct Compression Tableting of Powders into a Solid Oral Dosage Form"<br>Abstract:The treatment of enteric bacterial infections using oral bacteriophage therapy can be challenging since the harsh acidic stomach environment renders phages inactive during transit through the gastrointestinal tract. Solid oral dosage forms allowing site-specific gastrointestinal delivery of high doses of phages, e.g., using a pH or enzymatic trigger, would be a game changer for the nascent industry trying to demonstrate the efficacy of phages, including engineered phages for gut microbiome modulation in expensive clinical trials. Spray-drying is a scalable, low-cost process for producing pharmaceutical agents in dry powder form. Encapsulation of a model Salmonella-specific phage (Myoviridae phage Felix O1) was carried out using the process of spray-drying, employing a commercially available Eudragit S100^® pH-responsive anionic copolymer composed of methyl methacrylate-co-methacrylic acid formulated with trehalose. Formulation and processing conditions were optimised to improve the survival of phages during spray-drying, and their subsequent protection upon exposure to simulated gastric acidity was demonstrated. Addition of trehalose to the formulation was shown to protect phages from elevated temperatures and desiccation encountered during spray-drying. Direct compression of spray-dried encapsulated phages into tablets was shown to significantly improve phage protection upon exposure to simulated gastric fluid. The results reported here demonstrate the significant potential of spray-dried pH-responsive formulations for oral delivery of bacteriophages targeting gastrointestinal applications.<br>

《基于pH响应配方喷雾干燥（spray-drying）制备沙门氏菌特异性噬菌体Felix O1微囊及粉末直接压片制备固体口服制剂》补充信息文件<br>摘要：口服噬菌体（bacteriophage）疗法用于治疗肠道细菌性感染时往往面临挑战，因为胃部严苛的酸性环境会导致噬菌体在通过胃肠道的过程中失活。能够实现高剂量噬菌体胃肠道靶向递送的固体口服制剂（例如通过pH或酶触发释药），对于当前正试图在昂贵的临床试验中验证噬菌体（包括用于调控肠道菌群的工程化噬菌体（engineered phages））疗效的新兴行业而言，将是颠覆性的突破。喷雾干燥是一种可规模化、低成本制备干粉状药剂的工艺。本研究以沙门氏菌特异性模式噬菌体（肌尾噬菌体科（Myoviridae）噬菌体Felix O1）为对象，采用喷雾干燥工艺进行微囊化包埋，所用载体为市售的Eudragit S100^®——一种由甲基丙烯酸甲酯-甲基丙烯酸共聚而成的pH响应型阴离子共聚物，并辅以海藻糖（trehalose）进行配方配制。研究对配方与工艺参数进行了优化，以提升噬菌体在喷雾干燥过程中的存活率，并验证了其在模拟胃酸环境下可获得有效保护。实验结果表明，在配方中添加海藻糖可保护噬菌体免受喷雾干燥过程中高温与干燥脱水的损伤。将喷雾干燥得到的包埋噬菌体粉末直接压片，可显著提升噬菌体在模拟胃液中的存活率与保护效果。本研究结果表明，喷雾干燥制备的pH响应型配方用于靶向胃肠道的噬菌体口服递送，具有极高的应用潜力。