Repurposing of statins via inhalation to treat lung inflammatory conditions

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.

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“…Hence, alternative routes of statin administration are warranted to improve its efficacy. The repurposing of statins, as an inhaled therapy, is one such strategy as it delivers higher concentrations of drug to the lungs at lower drug dosages as compared to oral delivery 62, 63. There are increasing lines of evidence showing the potential and benefits of using inhaled statins in mouse models with inflammatory lung diseases 64-66.…”

Chinese Herbs and Repurposing Old Drugs as Therapeutic Agents in the Regulation of Oxidative Stress and Inflammation in Pulmonary Diseases

“…In several animal experiments, the inhalation of statins such as simvastatin pravastatin, rosuvastatin, pitavastatin, and atorvastatin induced better effects on anti-pulmonary inflammation. 232 Thus, statins could be efficacious in the treatment of lung inflammatory disorders and the development of inhalation formulations is warranted.…”

Karma of Cardiovascular Disease Risk Factors for Prevention and Management of Major Cardiovascular Events in the Context of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

“…Since hyperlipidemia is an independent risk factor for CVD, and since many patients with COPD die of CVDs, statins could have benefit in reducing mortality. Some authors suggest that statins, in addition to decreasing of serum cholesterol, may have anti-inflammatory effects on both pulmonary and systemic inflammation through inhibition of guanosine triphosphates and nuclear factor-κB that controls activation of inflammatory and matrix remodeling pathways (110). A meta-analysis of 15 articles with a total of 238,459 participants with COPD found that the use of statins was associated with a 31% reduced risk of MI (HR 0.69, 95% CI 0.49–0.99), but not of CVD mortality (111).…”