School of Life Sciences, University of Technology Sydney, Australia; Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney, Australia.
Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney, Australia; Respiratory Technology, Woolcock Institute of Medical Research and Faculty of Medicine and Health, The University of Sydney, Australia.
Adv Drug Deliv Rev. 2018 Aug;133:93-106. doi: 10.1016/j.addr.2018.06.005. Epub 2018 Jun 8.
Despite many therapeutic advancements over the past decade, the continued rise in chronic inflammatory lung diseases incidence has driven the need to identify and develop new therapeutic strategies, with superior efficacy to treat these diseases. Statins are one class of drug that could potentially be repurposed as an alternative treatment for chronic lung diseases. They are currently used to treat hypercholesterolemia by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, that catalyses the rate limiting step in the mevalonate biosynthesis pathway, a key intermediate in cholesterol metabolism. Recent research has identified statins to have other protective pleiotropic properties including anti-inflammatory, anti-oxidant, muco-inhibitory effects that may be beneficial for the treatment of chronic inflammatory lung diseases. However, clinical studies have yielded conflicting results. This review will summarise some of the current evidences for statins pleiotropic effects that could be applied for the treatment of chronic inflammatory lung diseases, their mechanisms of actions, and the potential to repurpose statins as an inhaled therapy, including a detailed discussion on their different physical-chemical properties and how these characteristics could ultimately affect treatment efficacies. The repurposing of statins from conventional anti-cholesterol oral therapy to inhaled anti-inflammatory formulation is promising, as it provides direct delivery to the airways, reduced risk of side effects, increased bioavailability and tailored physical-chemical properties for enhanced efficacy.
尽管在过去十年中取得了许多治疗进展，但慢性炎症性肺部疾病发病率的持续上升促使人们需要识别和开发新的治疗策略，以提高治疗这些疾病的疗效。他汀类药物是一类可能被重新用作慢性肺部疾病替代治疗的药物。它们目前通过抑制 3-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶来治疗高胆固醇血症，该酶催化甲羟戊酸生物合成途径中的限速步骤，是胆固醇代谢的关键中间产物。最近的研究发现，他汀类药物具有其他保护多效性特性，包括抗炎、抗氧化、粘液抑制作用，这可能有益于治疗慢性炎症性肺部疾病。然而，临床研究得出了相互矛盾的结果。本综述将总结他汀类药物多效性作用的一些现有证据，这些作用可应用于治疗慢性炎症性肺部疾病，包括其作用机制以及将他汀类药物重新用作吸入治疗的潜力，包括详细讨论它们的不同理化特性以及这些特性如何最终影响治疗效果。将他汀类药物从传统的抗胆固醇口服治疗重新用于吸入性抗炎制剂具有广阔前景，因为它可以直接将药物输送到气道，降低副作用风险，提高生物利用度，并针对增强疗效定制理化特性。
