Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment In COVID-19
Overview
Chemistry
Molecular Biology
Affiliations
At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. COVID-19 pathology is characterized by extreme inflammation and amplified immune response with activation of a cytokine storm. A subsequent progression to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can take place, which is often followed by death. The causes of these strong inflammatory responses in SARS-CoV-2 infection are still unknown. As uncontrolled pulmonary inflammation is likely the main cause of death in SARS-CoV-2 infection, anti-inflammatory therapeutic interventions are particularly important. Fenretinide N-(4-hydroxyphenyl) retinamide is a bioactive molecule characterized by poly-pharmacological properties and a low toxicity profile. Fenretinide is endowed with antitumor, anti-inflammatory, antiviral, and immunomodulating properties other than efficacy in obesity/diabetic pathologies. Its anti-inflammatory and antiviral activities, in particular, could likely have utility in multimodal therapies for the treatment of ALI/ARDS in COVID-19 patients. Moreover, fenretinide administration by pulmonary delivery systems could further increase its therapeutic value by carrying high drug concentrations to the lungs and triggering a rapid onset of activity. This is particularly important in SARS-CoV-2 infection, where only a narrow time window exists for therapeutic intervention.
The Sphingolipid-Signaling Pathway as a Modulator of Infection by SARS-CoV-2.
Fenizia S, Gaggini M, Vassalle C Curr Issues Mol Biol. 2023; 45(10):7956-7973.
PMID: 37886946 PMC: 10605018. DOI: 10.3390/cimb45100503.
Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19.
Alipour S, Mahmoudi L, Ahmadi F Drug Deliv Transl Res. 2022; 13(3):705-715.
PMID: 36260223 PMC: 9580423. DOI: 10.1007/s13346-022-01251-1.
Salvianolic acid B dry powder inhaler for the treatment of idiopathic pulmonary fibrosis.
Lu P, Li J, Liu C, Yang J, Peng H, Xue Z Asian J Pharm Sci. 2022; 17(3):447-461.
PMID: 35782322 PMC: 9237582. DOI: 10.1016/j.ajps.2022.04.004.
Hu S, Jiang S, Qi X, Bai R, Ye X, Xie T Drug Dev Res. 2021; 83(1):16-54.
PMID: 34762760 PMC: 8653368. DOI: 10.1002/ddr.21895.
Fenretinide inhibits vitamin A formation from β-carotene and regulates carotenoid levels in mice.
Miller A, Black M, Amengual J Biochim Biophys Acta Mol Cell Biol Lipids. 2021; 1867(2):159070.
PMID: 34742949 PMC: 8688340. DOI: 10.1016/j.bbalip.2021.159070.