Dexamethasone Controlled Release on TGF-ß1 Treated Vocal Fold Fibroblasts.

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-ß1. 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-ß1 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.

Enhanced adhesion of dopamine methacrylamide elastomers via viscoelasticity tuning.

We present a study on the effects of cross-linking on the adhesive properties of bio-inspired 3,4-dihydroxyphenylalanine (DOPA). DOPA has a unique catechol moiety found in adhesive proteins in marine organisms, such as mussels and polychaete, which results in strong adhesion in aquatic conditions. Incorporation of this functional group in synthetic polymers provides the basis for pressure-sensitive adhesives for use in a broad range of environments. A series of cross-linked DOPA-containing polymers were prepared by adding divinyl cross-linking agent ethylene glycol dimethacrylate (EGDMA) to monomer mixtures of dopamine methacrylamide (DMA) and 2-methoxyethyl acrylate (MEA). Samples were prepared using a solvent-free microwave-assisted polymerization reaction and compared to a similar series of cross-linked MEA materials. Cross-linking with EGDMA tunes the viscoelastic properties of the adhesive material and has the advantage of not reacting with the catechol group that is responsible for the excellent adhesive performance of this material. Adhesion strength was measured by uniaxial indentation tests, which indicated that 0.001 mol % of EGDMA-cross-linked copolymer showed the highest work of adhesion in dry conditions, but non-cross-linked DMA was the highest in wet conditions. The results suggest that there is an optimal cross-linking degree that displays the highest adhesion by balancing viscous and elastic behaviors of the polymer but this appears to depend on the conditions. This concentration of cross-linker is well below the theoretical percolation threshold, and we propose that subtle changes in polymer viscoelastic properties can result in significant improvements in adhesion of DOPA-based materials. The properties of lightly cross-linked poly(DMA-co-MEA) were investigated by measurement of the frequency dependence of the storage modulus (G') and loss modulus (G''). The frequency-dependence of G' and magnitude of G'' showed gradual decreases with the fraction of EGDMA. Loosely cross-linked DMA copolymers, containing 0% and 0.001 mol % of EGDMA-cross-linked copolymers, displayed rheological behavior appropriate for pressure-sensitive adhesives characterized by a higher G' at high frequencies and lower G' at low frequencies. Our results indicate that dimethacrylate cross-linking of DMA copolymers can be used to enhance the adhesive properties of this unique material.