The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress

Abstract

Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti‐inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post‐transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro‐inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.

Cardioprotective role of metformin against sodium arsenite‐induced oxidative stress, inflammation, and apoptosis

“…TNF-α, IL-6, and IL-1β are viewed as biomarkers of inflammation response, which typically lead to destruction of tissue. 28,29 The concentration of IL-6 and IL-1β corresponds well with the level of systemic inflammation and the seriousness of tissue damage and is believed to be related to postponed apoptosis. 30 TNF-α, IL-6, and IL-1β were incorporated into phagocytic incitement, chemokine creation, and variable impacts on cell development and death.…”

“…Inflammation is a biological reaction that enables the healing process of harmed tissues, such as expulsion of destructive impacts on the body. TNF‐α, IL‐6, and IL‐1β are viewed as biomarkers of inflammation response, which typically lead to destruction of tissue . The concentration of IL‐6 and IL‐1β corresponds well with the level of systemic inflammation and the seriousness of tissue damage and is believed to be related to postponed apoptosis .…”

Macrophage metabolic reprogramming during chronic lung disease

“…Rifampicin-loaded microspheres as a therapeutic approach for Mtb have been described 235 , and have been further refined to allow a one-step assembly for rifampicin containing microspheres 236 . Recently, aerosolised delivery of siRNA, which post-translationally downregulates gene expression, has been developed to target AMs specifically 237 , whilst mannose coated microspheres have been developed which exploit the phagocytotic activity of AMs 238 . Many of these delivery vehicles have been developed to transport antibiotics targeting intracellular AM bacterial infections, which are helpful for treating TB, however other drugs could be incorporated into aerosolised micro- or nano delivery systems.…”

Prospects for RNAi Therapy of COVID-19

“…Inhalational delivery of RNAi agents and dry powder formulations of siRNA was recently reviewed ( Dua et al, 2019 ; Keil and Merkel, 2019 ). In 2020, Fukushige et al (2020) described hyaluronic acid coated liposomes as spray freeze-dried nanoparticles for pulmonary delivery of siRNA in lung cancer as a superior alternative to non-modified liposomes.…”