Nanodrug delivery platform for glucocorticoid use in skeletal muscle injury

• Published in: Canadian journal of physiology and pharmacology Vol. 96; no. 7; pp. 681 - 689
• Main Authors: Sutariya, Vijaykumar, Tur, Jared, Kelly, Shannon, Halasz, Kathleen, Chapalamadugu, Kalyan C, Nimbalkar, Rohini, Pathak, Yashwant V, Weigel, Robert, Daviau, Todd, Webb, Travis, Cacace, Janice, Brotto, Marco, Tipparaju, Srinivas M
• Format: Journal Article
• Language: English
• Published: Ottawa NRC Research Press 01.07.2018; Canadian Science Publishing NRC Research Press
• Subjects: Anti-inflammatory agents; Arthritis; Bioavailability; Cell migration; Controlled release; Dexamethasone; Dosage and administration; Drug delivery systems; Drug therapy; Encapsulation; Glucocorticoids; Glycolic acid; Inflammation; L-Lactate dehydrogenase; Lactic acid; Lipopolysaccharides; Methods; Muscles; Musculoskeletal system; Nanoparticles; Pain management; Particle size; Pharmacology; Physical characteristics; Physiology; Polydispersity; Polylactide-co-glycolide; Scanning electron microscopy; Senescence; Skeletal muscle; Steroids; Sustained release; Toxicity
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2017-0795

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-coglycolic 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 [+ or -] 19.99 nm with polydispersity index of 0.14 [+ or -] 0.07. The nanoparticles encapsulation efficiency was 34.57% [+ or -] 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 [micro]mol/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.