Article ; Online: BRD4 targeting nanotherapy prevents lipopolysaccharide induced acute respiratory distress syndrome.
International journal of pharmaceutics
2021 Volume 601, Page(s) 120536
Abstract: Acute respiratory distress syndrome (ARDS) is a life threatening respiratory disease associated with pulmonary edema, alveolar dysfunction, hypoxia, and inflammatory cell accumulation. The most contagious form of COVID-19 associated with ARDS caused by ... ...
| Abstract | Acute respiratory distress syndrome (ARDS) is a life threatening respiratory disease associated with pulmonary edema, alveolar dysfunction, hypoxia, and inflammatory cell accumulation. The most contagious form of COVID-19 associated with ARDS caused by SARS-CoV-2. SARS-CoV-2 majorly produces the cytokine storm and severe lung inflammation and ultimately leads to respiratory failure. ARDS is a complex disease and there is no proper therapeutics for effective therapy. Still, there is a huge scope to identify novel targets to combat respiratory illness. In the current study, we have identified the epigenetic regulating protein BRD4 and developed siRNA based nanomedicine to treat the ARDS. The liposomes were prepared by thin-film hydration method, where BRD4 siRNA complexed with cationic lipid and exhibited 96.24 ± 18.01 nm size and stable even in the presence of RNase. BRD4 siRNA lipoplexes (BRD4-siRNA-LP) inhibited inflammatory cells in lungs and suppressed the lipopolysaccharide (LPS) induced the neutrophil infiltration and mast cell accumulation. Also, BRD4 siRNA based nanomedicine significantly reduced the LPS induced cytokine storm followed by inflammatory signaling pathways. Interestingly, BRD4-siRNA-LP suppressed the LPS-induced p65 and STAT3 nuclear translocation and ameliorated the lung inflammation. Thus, BRD4-siRNA-LP could be a plausible therapeutic option for treating ARDS and might be useful for combating the COVID-19 associated respiratory illness. |
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| MeSH term(s) | COVID-19 ; Cell Cycle Proteins ; Humans ; Lipopolysaccharides ; Nuclear Proteins ; Respiratory Distress Syndrome/drug therapy ; SARS-CoV-2 ; Transcription Factors/genetics | |||||
| Chemical Substances | BRD4 protein, human ; Cell Cycle Proteins ; Lipopolysaccharides ; Nuclear Proteins ; Transcription Factors | |||||
| Language | English | |||||
| Publishing date | 2021-03-27 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 428962-6 | |||||
| ISSN | 1873-3476 ; 0378-5173 | |||||
| ISSN (online) | 1873-3476 | |||||
| ISSN | 0378-5173 | |||||
| DOI | 10.1016/j.ijpharm.2021.120536 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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