Department of Pharmacy, China Pharmaceutical University, No.639, Longmian Avenue, Nanjing, 211198, People's Republic of China.
AAPS PharmSciTech. 2018 Nov;19(8):3670-3680. doi: 10.1208/s12249-018-1183-0. Epub 2018 Oct 18.
Nucleic acid-based therapeutics present huge potential in the treatment of pulmonary diseases ranging from lung cancer to asthma and chronic pulmonary diseases, which are often fatal and widely prevalent. The susceptibility of nucleic acids to degradation and the complex structure of lungs retard the effective pulmonary delivery of nucleic acid drug. To overcome these barriers, different strategies have been exploited to increase the delivery efficiency using chemically synthesized nucleic acids, vector encapsulation, proper formulation, and administration route. However, several limitations regarding off-target effects and immune stimulation of nucleic acid drugs hamper their translation into the clinical practice. Therefore, their successful clinical application will ultimately rely on well-developed carriers and methods to ensure safety and efficacy. In this review, we provide a comprehensive overview of the nucleic acid application for pulmonary diseases, covering action mechanism of the nucleic acid drugs, the novel delivery systems, and the current formulation for the administration to lungs. The latest advances of nucleic acid drugs under clinical evaluation to treat pulmonary disorders will also be detailed.
核酸治疗药物在治疗从肺癌到哮喘和慢性肺部疾病等肺部疾病方面具有巨大潜力，这些疾病通常是致命的且广泛存在的。核酸容易降解和肺部结构复杂，这阻碍了核酸药物在肺部的有效传递。为了克服这些障碍，人们利用化学合成的核酸、载体包封、适当的配方和给药途径等不同策略来提高传递效率。然而，核酸药物的脱靶效应和免疫刺激等问题限制了它们在临床实践中的转化。因此，它们的成功临床应用最终将取决于开发完善的载体和方法，以确保安全性和疗效。在这篇综述中，我们全面概述了核酸在肺部疾病中的应用，包括核酸药物的作用机制、新型传递系统以及肺部给药的现行制剂。我们还详细介绍了正在临床评估中用于治疗肺部疾病的核酸药物的最新进展。
