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Charlotte Schramm, Karolin Adler, Martin S. Spitzer, Kai Januschowski, Karl-Ullrich Bartz-Schmidt, Peter Szurman; Uv-crosslinked Hyaluronic Acid As An Intraocular Slow Release System For Dexamethasone. Invest. Ophthalmol. Vis. Sci. 2011;52(14):452.
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Aim of the study was to crosslink dexamethasone with hyaluronic acid using uv-light and to investigate if crosslinked hyaluronic acid could serve as an intraocular slow release system for dexamethasone resulting in a prolonged biological effect.
Different concentrations of dexamethasone (between 6 and 16 mg/ ml dexamethasone) and hyaluronic acid were crosslinked using uv-light. The cumulative release of dexamethasone was measured and quantified photometrically and by performing high-performance liquid chromatography (HPLC) over a period of two weeks. In order to asses the biocompatibility and whether there still was an anti-proliferative effect of dexamethasone after crosslinking a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) assay was performed using retinal pigment epithelium cells (RPE cells) and compared to untreated dexamethasone as control.
Via crosslinking solid three-dimensional dexamethasone-hyaluronic acid hydrogels could be generated. The release of dexamethasone was measured photometrically at a wavelength of 239 nm. Photometrical quantification of the release of dexamethasone revealed that within 24 hours almost all crosslinked dexamethasone was set free. In contrast, HPLC to quantify the release of dexamethasone showed that within 24 hours between 39 to 46 % of the crosslinked dexamethasone was set free (p< 0.05). The latter is in accordance with our observation that a slight haze of the hydrogels was detectable for a prolonged period of time.MTT-Test showed similar effects of crosslinked dexamethasone and untreated dexamethasone on RPE cells.
By crosslinking hyaluronic acid and dexamethasone a three-dimensional hydrogel can be generated which releases dexamethasone over more than 24 hours. However, in comparison to previous studies there was no difference between the release of dexamethasone from native to crosslinked hyaluronic acid. It could be shown that the released dexamethasone maintains its biological properties after the crosslinking procedure. Thus, uv-crosslinked hyaluronate may serve as intraocular release systems for anti-proliferative drugs which because of there very slow degradation may not cause intraocular pressure spikes like native hyaluronic acid.
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