Wang Yuncheng, Khanal Dipesh, Alreja Adit B, Yang Hang, Yk Chang Rachel, Tai Waiting, Li Mengyu, Nelson Daniel C, Britton Warwick J, Chan Hak-Kim
Advanced Drug Delivery Group, School of Pharmacy, University of Sydney, Sydney, NSW, Australia.
Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD, USA.
Int J Pharm. 2023 Mar 25;635:122679. doi: 10.1016/j.ijpharm.2023.122679. Epub 2023 Feb 3.
Endolysins are bacteriophage-encoded enzymatic proteins that have great potential to treat multidrug-resistant bacterial infections. Bacteriophage endolysins Cpl-1 and ClyJ-3 have shown promising antimicrobial activity against Streptococcus pneumoniae, which causes pneumonia in humans. This is the first study to investigate the feasibility of spray-dried endolysins Cpl-1 and ClyJ-3 with excipients to produce inhalable powders. The two endolysins were individually tested with leucine and sugar (lactose or trehalose) for spray drying method followed by characterization of biological and physico-chemical properties. A complete loss of ClyJ-3 bioactivity was observed after atomization of the liquid feed solution（before the drying process）, while Cpl-1 maintained its bioactivity in the spray-dried powders. Cpl-1 formulations containing leucine with lactose or trehalose showed promising physico-chemical properties (particle size, crystallinity, hygroscopicity, etc.) and aerosol performances (fine particle fraction values above 65%). The results indicated that endolysin Cpl-1 can be formulated as spray dried powders suitable for inhaled delivery to the lungs for the potential treatment of pulmonary infections.
内溶素是噬菌体编码的酶蛋白，在治疗多重耐药细菌感染方面具有巨大潜力。噬菌体内溶素Cpl-1和ClyJ-3已显示出对肺炎链球菌有良好的抗菌活性，肺炎链球菌可导致人类肺炎。这是第一项研究喷雾干燥的内溶素Cpl-1和ClyJ-3与辅料制成可吸入粉末的可行性的研究。分别用亮氨酸和糖（乳糖或海藻糖）对这两种内溶素进行喷雾干燥方法测试，随后对其生物学和物理化学性质进行表征。在液体进料溶液雾化后（干燥过程之前）观察到ClyJ-3的生物活性完全丧失，而Cpl-1在喷雾干燥粉末中保持其生物活性。含有亮氨酸与乳糖或海藻糖的Cpl-1制剂显示出良好的物理化学性质（粒径、结晶度、吸湿性等）和气溶胶性能（细颗粒分数值高于65%）。结果表明，内溶素Cpl-1可以制成喷雾干燥粉末，适合通过吸入递送至肺部，用于潜在的肺部感染治疗。
