Nano-drug delivery platform for glucocorticoid use in skeletal muscle injury.

Glucocorticoids are utilized for its anti-inflammatory properties in the skeletal muscle and arthritis. However, the major drawback with 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 bio-availability of the drug, in the present study we hypothesized that nano-delivery of dexamethasone will offer increased efficacy and decreased toxicity. The dexamethasone loaded PLGA (poly lactic-co-glycolic acid) 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 (PDI) 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 10nM nano-Dexamethasone-PLGA, however dexamethasone solution (1µM) was injurious to cells since the migration efficiency was decreased. In addition, the use of NP-Dexamethasone decreased LPS induced LDH release compared with dexamethasone solution. Taken together, the present study clearly demonstrates that delivery of PLGA-dexamethasone nano-particles to the skeletal muscle cells is beneficial for treating inflammation and skeletal muscle function.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author