Can bilirubin nanomedicine become a hope for the management of COVID-19?

Abstract

Bilirubin has been proven to possess significant anti-inflammatory, antioxidant and antiviral activities. Recently, it has been postulated as a metabolic hormone. Further, moderately higher levels of bilirubin are positively associated with reduced risk of cardiovascular diseases, diabetes, metabolic syndrome and obesity. However, due to poor solubility the therapeutic delivery of bilirubin remains a challenge. Nanotechnology offers unique advantages which may be exploited for improved delivery of bilirubin to the target organ with reduced risk of systemic toxicity. Herein, we postulate the use of intravenous administration or inhalational delivery of bilirubin nanomedicine (BNM) to combat systemic dysfunctions associated with COVID-19, owing to the remarkable preclinical efficacy and optimistic results of various clinical studies of bilirubin in non-communicable disorders. BNM may be used to harness the proven preclinical pharmacological efficacy of bilirubin against COVID-19 related systemic complications.

Keywords: Anti-inflammatory; Antioxidant; Bilirubin; Biliverdin; COVID-19; Nanomedicine.

Fig. 1

Respiratory airways exposure to coronavirus. Dendritic cells (DCs) in the respiratory airways capture, internalize, and display coronavirus on the cell surface of MHCII molecules. DCs migrate to the lymph node (LN) and encounter coronavirus-specific T cells. The DCs induce the differentiation of the T cells into Th2 cells. Th2 cells produce cytokines (IL-4, IL-5 and IL-13) that induce mucus production and smooth muscle contraction in the airways. This forms the basis of allergic airway sensitization and cytokine mediated lungs insufficiency. The figure was created with BioRender.com.

Fig. 2

Coronavirus get inhaled and travel to the respiratory airways. Once there, their stimulus damages the epithelium, which causes the release of different alarmins: IL-33, IL-25 and TSLP. ILC2, innate immune cells, are activated and release proinflammatory type 2 cytokines, such as IL-5 and IL-13 for the recruitment of eosinophils and mucus production, respectively. T helper cells, adaptive immune cells, are activated in an antigen-dependent manner via dendritic cells and cause major respiratory problems, including fibrotic lungs and inflammation. The figure was created with BioRender.com.

Fig. 3

Administration of BNM by various routes and their advantages. Part of the figure were adapted and reproduced from reference under the Creative Commons Attribution License (CCBY).