Abstract: Severe steroid-resistant asthma (SSR) patients do not respond to the corticosteroid therapies due to the heterogeneity, and genome-wide variations. However, there are very limited reports pertinent to the molecular signaling underlying SSR and making pharmacologists, and formulation scientists to identify the effective therapeutic targets in order to produce novel therapies using novel drug delivery systems (NDDS). We have substantially searched literature for the peer-reviewed and published reports delineating the role of glucocorticoid-altered gene expression, and the mechanisms responsible for SSR asthma, and NDDS for treating SSR asthma using public databases PubMed, National Library of Medicine (NLM), google scholar, and medline. Subsequently, we described reports underlying the SSR pathophysiology through several immunological and inflammatory phenotypes. Furthermore, various therapeutic strategies and the role of signaling pathways such as mORC1-STAT3-FGFBP1, NLRP3 inflammasomes, miR-21/PI3K/HDAC2 axis, PI3K were delineated and these can be considered as the therapeutic targets for mitigating the pathophysiology of SSR asthma. Finally, the possibility of nanomedicine-based formulation and their applications in order to enhance the long term retention of several antioxidant and anti-asthmatic drug molecules as a significant therapeutic modality against SSR asthma was described vividly.
Keywords: natural products, steroid resistance, asthma, inflammation, molecular signaling, nanomedicine, novel drug delivery systems