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吸入递呈抗假单胞菌噬菌体以应对超级细菌引起的呼吸道感染。

Inhaled Delivery of Anti-Pseudomonal Phages to Tackle Respiratory Infections Caused by Superbugs.

机构信息

Advanced Drug Delivery Group, Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

出版信息

J Aerosol Med Pulm Drug Deliv. 2022 Apr;35(2):73-82. doi: 10.1089/jamp.2021.0045. Epub 2021 Dec 30.

DOI:10.1089/jamp.2021.0045
PMID:34967686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8982117/
Abstract

Respiratory infections are increasingly difficult to treat due to the emergence of multidrug-resistant bacteria. Rediscovery and implementation of inhaled bacteriophage (phage) therapy as a standalone or supplement to antibiotic therapy is becoming recognized as a promising solution to combating respiratory infections caused by these superbugs. To ensure maximum benefit of the treatment, phages must remain stable during formulation as a liquid or powder and delivery using a nebulizer or dry powder inhaler. -targeting PEV phages were used as model phages to assess the feasibility of aerosolizing biologically viable liquid formulations using commercial nebulizers in the presence and absence of inhaled antibiotics. The advantages of powder formulations were exploited by spray drying to produce inhalable powders containing PEV phages with and without the antibiotic ciprofloxacin. The produced phage PEV20 and PEV20-ciprofloxacin powders remained stable over long-term storage and exhibited significant bacterial killing activities in a mouse lung infection model. These studies demonstrated that inhaled phage (-antibiotic) therapy has the potential to tackle respiratory infections caused by superbugs.

摘要

呼吸道感染由于多药耐药菌的出现而越来越难以治疗。重新发现和实施吸入噬菌体(噬菌体)治疗作为抗生素治疗的独立或补充方法,正被认为是对抗这些超级细菌引起的呼吸道感染的有前途的解决方案。为了确保治疗的最大益处,噬菌体在作为液体或粉末进行配方以及使用雾化器或干粉吸入器进行输送时必须保持稳定。-靶向 PEV 噬菌体被用作模型噬菌体,以评估在存在和不存在吸入性抗生素的情况下,使用商业雾化器将生物上可行的液体制剂气溶胶化的可行性。通过喷雾干燥来利用粉末制剂的优势,以生产含有 PEV 噬菌体和抗生素环丙沙星的可吸入粉末。生产的噬菌体 PEV20 和 PEV20-环丙沙星粉末在长期储存期间保持稳定,并在小鼠肺部感染模型中表现出显著的杀菌活性。这些研究表明,吸入噬菌体(-抗生素)治疗有可能解决由超级细菌引起的呼吸道感染。

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本文引用的文献

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Dry powder pharmaceutical biologics for inhalation therapy.干粉吸入治疗用药物制剂。
Adv Drug Deliv Rev. 2021 May;172:64-79. doi: 10.1016/j.addr.2021.02.017. Epub 2021 Mar 8.
2
Phage cocktail powder for Pseudomonas aeruginosa respiratory infections.用于铜绿假单胞菌呼吸道感染的噬菌体鸡尾酒粉剂。
Int J Pharm. 2021 Mar 1;596:120200. doi: 10.1016/j.ijpharm.2021.120200. Epub 2021 Jan 21.
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Synergistic activity of phage PEV20-ciprofloxacin combination powder formulation-A proof-of-principle study in a P. aeruginosa lung infection model.噬菌体 PEV20-环丙沙星联合粉末制剂的协同作用:在铜绿假单胞菌肺部感染模型中的原理研究。
Eur J Pharm Biopharm. 2021 Jan;158:166-171. doi: 10.1016/j.ejpb.2020.11.019. Epub 2020 Nov 27.
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Pharmacokinetics and Time-Kill Study of Inhaled Antipseudomonal Bacteriophage Therapy in Mice.小鼠吸入抗铜绿假单胞菌噬菌体疗法的药代动力学和时间杀菌研究
Antimicrob Agents Chemother. 2020 Dec 16;65(1). doi: 10.1128/AAC.01470-20.
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Contemporary Formulation Development for Inhaled Pharmaceuticals.当代吸入式药物制剂的发展。
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Overcoming challenges for development of amorphous powders for inhalation.克服吸入用无定形粉末开发的挑战。
Expert Opin Drug Deliv. 2020 Nov;17(11):1583-1595. doi: 10.1080/17425247.2020.1813105. Epub 2020 Aug 31.
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Bioeng Transl Med. 2020 Apr 14;5(2):e10159. doi: 10.1002/btm2.10159. eCollection 2020 May.
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Inhalable combination powder formulations of phage and ciprofloxacin for P. aeruginosa respiratory infections.可吸入联合噬菌体和环丙沙星的粉末制剂治疗铜绿假单胞菌呼吸道感染。
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Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus.利用工程噬菌体治疗播散性耐药脓肿分枝杆菌感染的患者。
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