PURPOSE: The aims of this study were to assess the trans-scleral delivery of dexamethasone phosphate (DexP) with a prototype lens device and a formulation comprising a vasoconstrictor and to determine the efficacy of this delivery system in treating experimentally induced uveitis in a rabbit model. METHODS: Passive trans-scleral delivery was performed on New Zealand white rabbits in vivo, using the lens device and a formulation of 0.034 M oxymetazoline (OMZ, the vasoconstrictor) and 0.5 M of dexamethasone sodium phosphate (DexNaP). Trans-scleral delivery of DexP without OMZ was the control. The amounts of DexP delivered into the eye and its distributions in the eye were determined by dissection of the eye and high-performance liquid chromatography assay in the pharmacokinetics study. The efficacy of the DexP delivery system in treating lipopolysaccharide-induced uveitis was also evaluated in the rabbit model in vivo. The effect of OMZ upon DexP delivery and its treatment efficacy was studied by comparing the DexP results with and without OMZ. RESULTS: In the pharmacokinetics study, the amounts of DexP delivered into the eye using the lens system with OMZ were significantly higher than those without OMZ. The results in the efficacy study showed a better treatment outcome with OMZ to relieve the symptoms of endotoxin-induced uveitis in rabbits. CONCLUSIONS: The potential of vasoconstrictors to enhance eye disease treatments in passive trans-scleral drug delivery was demonstrated. The higher DexP level in the eye and the improvement of the outcome in the efficacy study in the presence of the vasoconstrictor are consistent with the hypothesis that the vasoconstrictor enhances drug delivery by decreasing clearance.
PURPOSE: The aims of this study were to assess the trans-scleral delivery of dexamethasone phosphate (DexP) with a prototype lens device and a formulation comprising a vasoconstrictor and to determine the efficacy of this delivery system in treating experimentally induced uveitis in a rabbit model. METHODS: Passive trans-scleral delivery was performed on New Zealand white rabbits in vivo, using the lens device and a formulation of 0.034 M oxymetazoline (OMZ, the vasoconstrictor) and 0.5 M of dexamethasonesodium phosphate (DexNaP). Trans-scleral delivery of DexP without OMZ was the control. The amounts of DexP delivered into the eye and its distributions in the eye were determined by dissection of the eye and high-performance liquid chromatography assay in the pharmacokinetics study. The efficacy of the DexP delivery system in treating lipopolysaccharide-induced uveitis was also evaluated in the rabbit model in vivo. The effect of OMZ upon DexP delivery and its treatment efficacy was studied by comparing the DexP results with and without OMZ. RESULTS: In the pharmacokinetics study, the amounts of DexP delivered into the eye using the lens system with OMZ were significantly higher than those without OMZ. The results in the efficacy study showed a better treatment outcome with OMZ to relieve the symptoms of endotoxin-induced uveitis in rabbits. CONCLUSIONS: The potential of vasoconstrictors to enhance eye disease treatments in passive trans-scleral drug delivery was demonstrated. The higher DexP level in the eye and the improvement of the outcome in the efficacy study in the presence of the vasoconstrictor are consistent with the hypothesis that the vasoconstrictor enhances drug delivery by decreasing clearance.
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