Nanodrug delivery platform for glucocorticoid use in skeletal muscle injury

Can J Physiol Pharmacol. 2018 Jul;96(7):681-689. doi: 10.1139/cjpp-2017-0795. Epub 2018 May 14.

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.

Keywords: PLGA; dexamethasone; dexaméthasone; muscle squelettique; nanoparticles; nanoparticules; skeletal muscle.

MeSH terms

  • Animals
  • Biological Availability
  • Cell Line
  • Cell Survival / drug effects
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Drug Compounding / methods*
  • Drug Liberation
  • Glucocorticoids / pharmacology*
  • Glucocorticoids / therapeutic use
  • Lactic Acid / chemistry
  • Mice
  • Microscopy, Electron, Transmission
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / injuries
  • Myoblasts / drug effects
  • Myositis / drug therapy*
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Wound Healing / drug effects*

Substances

  • Glucocorticoids
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Dexamethasone