Food and Drug Department, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy.
Curr Pharm Des. 2021;27(12):1436-1452. doi: 10.2174/1381612827666210122143214.
Drug-resistant tuberculosis (TB) can be considered the man-made result of interrupted, erratic or inadequate TB therapy. As reported in WHO data, resistant Mycobacterium tuberculosis (Mtb) strains continue to constitute a public health crisis. Mtb is naturally able to survive host defence mechanisms and to resist most antibiotics currently available. Prolonged treatment regimens using the available first-line drugs give rise to poor patient compliance and a rapid evolution of strains resistant to rifampicin only or to both rifampicin and isoniazid (multi drug-resistant, MDR-TB). The accumulation of mutations may give rise to extensively drug-resistant strains (XDR-TB), i.e. strains with resistance also to fluoroquinolones and to the injectable aminoglycoside, which represent the second-line drugs. Direct lung delivery of anti-tubercular drugs, as an adjunct to conventional routes, provides high concentrations within the lungs, which are the intended target site of drug delivery, representing an interesting strategy to prevent or reduce the development of drug-resistant strains. The purpose of this paper is to describe and critically analyse the most recent and advanced results in the formulation development of WHO second-line drug inhalation products, with particular focus on dry powder formulation. Although some of these formulations have been developed for other lung infectious diseases (Pseudomonas aeruginosa, nontuberculous mycobacteria), they could be valuable to treat MDR-TB and XDR-TB.
耐药结核病（TB）可被视为中断、不稳定或不充分的 TB 治疗的人为结果。据世界卫生组织（WHO）的数据报告，耐药结核分枝杆菌（Mtb）菌株继续构成公共卫生危机。Mtb 能够自然地抵御宿主防御机制，并抵抗目前大多数可用的抗生素。使用现有一线药物进行长期治疗方案会导致患者依从性差，并且对利福平或利福平加异烟肼（耐多药，MDR-TB）仅具有耐药性的菌株迅速演变。突变的积累可能导致广泛耐药菌株（XDR-TB），即对氟喹诺酮类和注射用氨基糖苷类也具有耐药性的菌株，这些是二线药物。将抗结核药物直接递送至肺部，作为常规途径的辅助手段，可在肺部提供高浓度的药物，这是药物递送的预期靶部位，代表了预防或减少耐药菌株发展的一种有趣策略。本文的目的是描述和批判性分析 WHO 二线药物吸入产品制剂开发的最新和最先进的结果，特别关注干粉制剂。尽管其中一些制剂是为治疗其他肺部传染病（铜绿假单胞菌、非结核分枝杆菌）而开发的，但它们可能对治疗 MDR-TB 和 XDR-TB 具有重要价值。
