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In vitro testing of fluticasone drug delivery system for inflammatory injury and repair
Author(s) -
Tipparaju Srinivas,
Kelly Shan,
Weigel Robert,
Halasz Kathleen,
Tur Jared,
Brotto Marco,
Sutariya Vijaykumar
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.868.16
Subject(s) - inflammation , pharmacology , drug delivery , glucocorticoid , in vitro , fluticasone , chemistry , medicine , immunology , biochemistry , corticosteroid , organic chemistry
Glucocorticoids such as dexamethasone and fluticasone have potent anti‐inflammatory properties, but they also have serious side effects when used for extended periods or even at higher doses. For enhanced drug delivery and to test whether glucocorticoids are able to provide benefits at lower doses we developed a new nano‐drug delivery system (called Nano‐Gluco) and tested it in vitro in a model of muscle cell injury and repair. We characterized Nano‐Gluco for its physical and chemical characteristics. We utilized zeta potential, particle size analysis, scanning electron microscopy and differential scanning calorimeter to evaluate Nano‐Gluco. To test the efficacy of the system, we used the LPS induced cellular injury model. We demonstrated that Lactate dehydrogenase (LDH) release was significantly lower in positive controls glucocorticoid treated cells compared with LPS alone. In support for the benefits Nano‐Gluco, it allowed similar protection of cells in vitro at a much lower concentration than glucocorticoids alone. We next utilized the LPS induced injury model with C2C12 (murine myoblasts) cells to identify the effects injury and repair, as well as inflammation signaling. At the molecular level, we tested key inflammatory markers such as NFKb, TNFα, IL1β along with other cell markers such as p27, FOXO for the beneficial effects of steroids in muscle cell repair and inflammation. These markers confirmed the beneficial effects of employing Nano‐Gluco. Overall, we demonstrate that our new Nano‐Gluco system provides a highly efficient method for delivery of glucocorticoids to cells for achieving anti‐inflammatory properties at a much lower concentration compared with current glucocorticoid preparation. We are now moving into animal pre‐clinical studies to advance the use Nano‐Gluco in humans. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .