Chalmers James D, van Ingen Jakko, van der Laan Roald, Herrmann Jean-Louis
Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
Dept of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
Eur Respir Rev. 2021 Jul 20;30(161). doi: 10.1183/16000617.0010-2021. Print 2021 Sep 30.
Nontuberculous mycobacterial (NTM) pulmonary disease is a chronic respiratory infection associated with declining lung function, radiological deterioration and significantly increased morbidity and mortality. Patients often have underlying lung conditions, particularly bronchiectasis and COPD. NTM pulmonary disease is difficult to treat because mycobacteria can evade host defences and antimicrobial therapy through extracellular persistence in biofilms and sequestration into macrophages. Management of NTM pulmonary disease remains challenging and outcomes are often poor, partly due to limited penetration of antibiotics into intracellular spaces and biofilms. Efficient drug delivery to the site of infection is therefore a key objective of treatment, but there is high variability in lung penetration by antibiotics. Inhalation is the most direct route of delivery and has demonstrated increased efficacy of antibiotics like amikacin compared with systemic administration. Liposomes are small, artificial, enclosed spherical vesicles, in which drug molecules can be encapsulated to provide controlled release, with potentially improved pharmacokinetics and reduced toxicity. They are especially useful for drugs where penetration of cell membranes is essential. Inhaled delivery of liposomal drug solutions can therefore facilitate direct access to macrophages in the lung where the infecting NTM may reside. A range of liposomal drugs are currently being evaluated in respiratory diseases.
非结核分枝杆菌（NTM）肺病是一种慢性呼吸道感染，与肺功能下降、影像学恶化以及发病率和死亡率显著增加相关。患者通常有潜在的肺部疾病，尤其是支气管扩张症和慢性阻塞性肺疾病（COPD）。NTM肺病难以治疗，因为分枝杆菌可通过在生物膜中细胞外持续存在以及被巨噬细胞隔离来逃避宿主防御和抗菌治疗。NTM肺病的管理仍然具有挑战性，且治疗结果往往不佳，部分原因是抗生素进入细胞内空间和生物膜的渗透率有限。因此，将药物有效递送至感染部位是治疗的关键目标，但抗生素在肺部的渗透率差异很大。吸入是最直接的给药途径，与全身给药相比，已证明阿米卡星等抗生素的疗效有所提高。脂质体是小的、人工合成的、封闭的球形囊泡，药物分子可包裹在其中以实现控释，可能改善药代动力学并降低毒性。它们对于细胞膜穿透至关重要的药物尤其有用。因此，吸入脂质体药物溶液可促进直接接触肺部可能存在感染性NTM的巨噬细胞。目前正在对一系列脂质体药物进行呼吸系统疾病方面的评估。
