Dexamethasone Controlled Release on TGF-β1 Treated Vocal Fold Fibroblasts

Ann Otol Rhinol Laryngol. 2015 Jul;124(7):572-8. doi: 10.1177/0003489415570933. Epub 2015 Feb 9.

Abstract

Objective: Corticosteroids may be beneficial in treating vocal fold scarring. Current drug delivery methods do not permit controlled corticosteroid release. Here we investigate the effects of poly-lactic-co-glycolic acid (PLGA) microparticles loaded with the corticosteroid dexamethasone in reducing collagen synthesis and inflammation in vocal fold fibroblasts treated with and without TGF-β1.

Study design: Experimental, in vitro study.

Methods: PLGA microparticles of differing molecular weight and terminating moieties were synthesized using a hydrogel template method. The release of dexamethasone was characterized from these microparticles over 4 days. Based on the release studies, ester-terminated low molecular weight PLGA microparticles were loaded with dexamethasone and applied to TGF-β1 treated vocal fold fibroblasts for 4 days. Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assays (ELISAs) were used to assess the effects of released dexamethasone on collagen synthesis and inflammatory mediators.

Results: COL3A1 and COL1A2 were significantly down-regulated after exposure to ester-terminated low molecular weight PLGA microparticles loaded with dexamethasone. The loaded microparticles also reduced interleukin-6 synthesis.

Conclusion: These data show promise in using a PLGA microparticle-based delivery system to control dexamethasone release over 4 days. Our findings lay the groundwork for developing more effective treatments for vocal fold scarring.

Keywords: PLGA microparticles; dexamethasone; drug delivery; vocal fold scar.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biocompatible Materials
  • Cells, Cultured
  • Cicatrix / drug therapy
  • Cicatrix / metabolism
  • Cicatrix / pathology
  • Collagen / biosynthesis
  • Collagen / genetics
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Delayed-Action Preparations
  • Dexamethasone / administration & dosage*
  • Drug Carriers
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Glucocorticoids / administration & dosage
  • Humans
  • Lactic Acid*
  • Polyglycolic Acid*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymerase Chain Reaction
  • Transforming Growth Factor beta1 / drug effects*
  • Transforming Growth Factor beta1 / metabolism
  • Vocal Cord Dysfunction / drug therapy*
  • Vocal Cord Dysfunction / metabolism
  • Vocal Cord Dysfunction / pathology
  • Vocal Cords / drug effects
  • Vocal Cords / metabolism
  • Vocal Cords / pathology*

Substances

  • Biocompatible Materials
  • Cytokines
  • Delayed-Action Preparations
  • Drug Carriers
  • Glucocorticoids
  • Transforming Growth Factor beta1
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Dexamethasone
  • Collagen