Dexamethasone Controlled Release on TGF-β1 Treated Vocal Fold Fibroblasts

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.

Effects of corticosteroids vs halofuginone on vocal fold wound healing in an ovine model

“…A previous study revealed decreased collagen deposition in an injured rabbit VF model after dexamethasone injection 9 . Significant depression of collagen gene expression was noted 9 . In a clinical study, Wang et al identified 22 patients that developed VF fibrosis following microlaryngeal excisional surgeries 10 .…”

Phlorotannins ameliorate extracellular matrix production in human vocal fold fibroblasts and prevent vocal fold fibrosis via aerosol inhalation in a laser‐induced fibrosis model

“…Our results revealed that phlorotannins significantly suppressed the expression level of COL I and cell migration in TGFβ-stimulated hVFFs without exhibiting cytotoxicity, showing an inhibitory efficiency similar to treatment with 0.2 μg/ml MMC. A previous study reported that 1% w/v dexamethasone-loaded poly-lactic-coglycolic acid microparticles were less potent than phlorotannins isolated from E. cava (Kosinski, Pothen, Panitch, & Sivasankar, 2015).…”

“…Our results revealed that phlorotannins significantly suppressed the expression level of COL I and cell migration in TGF‐β‐stimulated hVFFs without exhibiting cytotoxicity, showing an inhibitory efficiency similar to treatment with 0.2 μg/ml MMC. A previous study reported that 1% w/v dexamethasone‐loaded poly‐lactic‐ co ‐glycolic acid microparticles were less potent than phlorotannins isolated from E. cava (Kosinski, Pothen, Panitch, & Sivasankar, 2015). Additionally, hepatocyte growth factor and interleukin‐6 have demonstrated antifibrotic activity at concentrations lower than phlorotannins by inhibiting the expression level of fibrotic markers, but their activity was less efficient (Vyas, Ishikawa, Duflo, Chen, & Thibeault, 2010).…”

Towards an in vitro fibrogenesis model of human vocal fold scarring

“…In a study by Kosinski et al antifibrotic effects of dexamethasone were tested in immortalized human VF fibroblasts by quantitative polymerase chain reaction (qPCR) for mRNA of collagen [ 19 ]. Comparable methods were used by Suehiro et al in a study with rat VF fibroblasts [ 20 ].…”