Glucocorticoids are utilized for their anti-inflammatory properties in the skeletal muscle and arthritis. However, the major drawback of use of glucocorticoids is that it leads to senescence and toxicity. Therefore, based on the idea that decreasing particle size allows for increased surface area and bioavailability of the drug, in the present study, we hypothesized that nanodelivery of dexamethasone will offer increased efficacy and decreased toxicity. The dexamethasone-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared using nanoprecipitation method. The morphological characteristics of the nanoparticles were studied under scanning electron microscope. The particle size of nanoparticles was 217.5 ± 19.99 nm with polydispersity index of 0.14 ± 0.07. The nanoparticles encapsulation efficiency was 34.57% ± 1.99% with in vitro drug release profile exhibiting a sustained release pattern over 10 days. We identified improved skeletal muscle myoblast performance with improved closure of the wound along with increased cell viability at 10 nmol/L nano-dexamethasone-PLGA. However, dexamethasone solution (1 μmol/L) was injurious to cells because the migration efficiency was decreased. In addition, the use of dexamethasone nanoparticles decreased lipopolysaccharide-induced lactate dehydrogenase release compared with dexamethasone solution. Taken together, the present study clearly demonstrates that delivery of PLGA-dexamethasone nanoparticles to the skeletal muscle cells is beneficial for treating inflammation and skeletal muscle function.

Glucocorticoids, such as fluticasone propionate (FP), are used for the treatment of inflammation and alleviation of nasal symptoms and allergies, and as an antipruritic. However, both short- and long-term therapeutic use of glucocorticoids can lead to muscle weakness and atrophy. In the present study, we evaluated the feasibility of the nanodelivery of FP with poly(dl-lactide-co-glycolide) (PLGA) and tested in vitro function. FP-loaded PLGA nanoparticles were prepared via nanoprecipitation and morphological characteristics were studied via scanning electron microscopy. FP-loaded nanoparticles demonstrated an encapsulation efficiency of 68.6% ± 0.5% with a drug loading capacity of 4.6% ± 0.04%, were 128.8 ± 0.6 nm in diameter with a polydispersity index of 0.07 ± 0.008, and displayed a zeta potential of –19.4 ± 0.7. A sustained in vitro drug release pattern was observed for up to 7 days. The use of fluticasone nanoparticle decreased lipopolysaccharide (LPS)-induced lactate dehydrogenase release compared with LPS alone in C2C12 treated cells. FP also decreased expression of LPS-induced inflammatory genes in C2C12 treated cells as compared with LPS alone. Taken together, the present study demonstrates in vitro feasibility of PLGA-FP nanoparticle delivery to the skeletal muscle cells, which may be beneficial for treating inflammation.

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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.

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