Physicochemical characterization of pre-clinical samples of a bacteriophage therapy spray-on patch for the treatment of COVID-19-related pressure injury resistant infections

冠状病毒大流行使压力性损伤成为人们关注的焦点。压力性损伤的发生率在患者和卫生专业人员中都大幅上升。这是由于全球ICU入院人数增加，对机械通风的需求大幅增加，更多地使用俯卧位治疗急性呼吸窘迫综合征，以及个人防护设备和医疗器械的使用急剧增加。压力损伤容易受到机会性多药耐药感染(MDR)的影响，可导致延误治疗、败血症、骨髓炎、截肢和死亡。对于新冠肺炎患者中血管有限区域的感染，多药耐药菌株经常报告抗生素治疗失败和疗效降低。抗生素疗法的替代或补充是使用噬菌体来靶向细菌感染。人体内对噬菌体的管理需要一个适当的递送系统。在生理条件下产生稳定、无毒的喷雾剂是将噬菌体安全地转移到临床的一种新方法。为此，我们将噬菌体鸡尾酒包裹在以氨基酸为基础的可生物降解聚合物中，以延长噬菌体在损伤部位的输送。2020年与FDA举行了IND前会议，以建立Phagelux产品PL-03-BM的全面CMC和临床计划。在这个合作研究项目中，我们的目标是对微囊化噬菌体的工程和临床前批次进行表征，以澄清与CMC相关的问题，并进一步阐明用于治疗和预防压疮伤口感染的整体药物开发计划PL-03-BM。

The cororonavirus pandemic has brought pressure injuries into sharp focus. The incidence of pressure injuries has dramatically risen amongst patients and health professionals alike. This is due by the global increase in ICU admissions, considerable rise in the need of mechanical ventilation, increased use of prone positioning to treat acute respiratory distress syndrome, and sharp increase in the use of personal protective equipment and medical devices. Pressure injuries susceptible to opportunistic multi-drug resistant infections (MDR) can result in delayed treatment, septicemia, osteomyelitis, amputation, and death. Failure and reduced efficacy of antibiotic treatment are frequently reported for MDR strains for infections located in areas of limited vascularization in COVID-19 patients. An alternative or supplement to antibiotic therapy is the use of bacteriophages to target bacterial infections. Administration of phages in humans requires an appropriate delivery system. The production of stable, non-toxic spray under physiological conditions constitutes a novel approach for the safe translation of bacteriophages to the clinic. To this end we encapsulated the bacteriophage cocktail in amino acid-based biodegradable polymers for a prolonged delivery of phages at the site of injury. A pre-IND meeting was held with the FDA in 2020 to establish a comprehensive CMC and clinical program for Phagelux product PL-03-BM. In this collaborative research project, we aim to characterize engineering and preclinical batches of microencapsulated phages in order to clarify issues related to CMC and further the overall drug development program PL-03-BM for the treatment and prevention of pressure ulcer wound infections.