Nanodrug delivery platform for glucocorticoid use in skeletal muscle injury

Abstract

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.

Identification of thiostrepton as a pharmacological approach to rescue misfolded alpha-sarcoglycan mutant proteins from degradation

“…Firstly, this is because THSP is a veterinarian drug with no human toxicology reports, requiring several complementary investigations in animal models in order to safeguard human administration. Secondly, THSP is mainly used through topical administration, requiring optimization of its administration route by, for example, using nanoparticles to target muscles and limit potential off-target side effects 32 . Even though clinical treatment may be some way off, our results describe a method for the identification of new treatments for hundreds of diseases involving misfolded proteins and hope for LGMD2D patients who remain without curative treatment.…”

Surface‐enhanced Raman spectroscopy for successful probing of itraconazole within poly(lactic‐co‐glycolic acid) nanoparticles

“…This is due to both the colloidal characteristic of the NP system and the typical lower drug content. Overall, such an investigation is usually carried out by separating out the polymeric‐based NPs from nonencapsulated or nonadsorbed bioactive molecule using ultracentrifugation or ultrafiltration . Nonetheless, using the above‐mentioned techniques do not provide an efficient separation of the bioactive molecule, thus leading to significant error while evaluating the drug's encapsulation yield.…”