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William F. Mieler, Alyssa Appel, Sanja B. Turturro, Bin Jiang, Victor Perez-Luna, Eric Brey, Jennifer J. Kang Mieler; Efficacy Of Dexamethasone Sodium Phosphate Thermo-responsive Hydrogel Treatment In Endotoxin-induced Uveitis Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2752.
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To increase bioavailability of dexamethasone sodium phosphate (DSP), newly developed thermo-responsive hydrogel was used to encapsulate DSP. The main objective of this study was to investigate the efficacy of released DSP from thermo-responsive hydrogel delivery system in endotoxin-induced uveitis (EIU) model.
Thermo-responsive hydrogel was synthesized using poly(N-isopropylacrylamide) (PNIPAAm) and crosslinked with polyethylene glycols-diacrylate (PEG-DA) and 5% A-lysine and 15% NtBAAM. DSP (4 mg/ml) was loaded by equilibrating hydrogel in DSP solution overnight. Intravitreal injections of Lipopolysaccharides (LPS) from Salmonella Typhimurium were given to adult Lewis rats. After 24 hours post-LPS injection, 5 µl of DSP loaded thermo-responsive hydrogel was given intravitreally. Results were compared to control group 1 that received no treatment after LPS injection and control group 2 that received intravitreal injection of DSP only. In vivo imaging of the retina was performed using scanning laser ophthalmoscope (SLO). Evaluation was obtained at 24, 48, 72 and 144 hours post-LPS injection.
Approximately 24 hours after the LPS injection, severe clinical signs of inflammation such as dilation of retinal vessels and haziness were observed. There was on average 45% vasodilation of retinal vessels after the LPS injection. Untreated eyes continued to exhibit pronounced signs of inflammation throughout the investigated period. DSP-thermo-responsive hydrogel treated eyes showed ~15% decreased in vasodilation by 48 hours. The image quality (improvement in haziness) was significantly improved by 48 hours and continued to improve by 144 hours post-LPS injection. DSP only treated eyes showed similar results as DSP-thermo-responsive hydrogel treatment.
Current results suggest that DSP can be incorporated into thermo-responsive hydrogel for localized delivery and can release active DSP to have positive impact on experimental uveitis. The system provides relatively non-invasive delivery options and promising new platform for sustained delivery of dexamethasone sodium phosphate.
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