Repurposing of statins via inhalation to treat lung inflammatory conditions

Peta Bradbury; Daniela Traini; Alaina J Ammit; Paul M Young; Hui Xin Ong

doi:10.1016/j.addr.2018.06.005

Repurposing of statins via inhalation to treat lung inflammatory conditions

Adv Drug Deliv Rev. 2018 Aug:133:93-106. doi: 10.1016/j.addr.2018.06.005. Epub 2018 Jun 8.

Authors

Peta Bradbury¹, Daniela Traini², Alaina J Ammit¹, Paul M Young², Hui Xin Ong³

Affiliations

¹ School of Life Sciences, University of Technology Sydney, Australia; Woolcock Emphysema Centre, Woolcock Institute of Medical Research, University of Sydney, Australia.
² 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.
³ 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. Electronic address: ong.hui@sydney.edu.au.

PMID: 29890243
DOI: 10.1016/j.addr.2018.06.005

Abstract

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.

Keywords: Anti-inflammatory; Anti-oxidant; Inhalation; Muco-inhibition; Respiratory diseases; Statins.

Publication types

Review

MeSH terms

Administration, Inhalation
Drug Repositioning*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Inflammation / drug therapy*
Lung Diseases / drug therapy*

Substances

Hydroxymethylglutaryl-CoA Reductase Inhibitors