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P. Tyagi, V. Rao, C. O'Neill, T. Gadek, U. B. Kompella; Eye Drop and Microparticle Formulations of SAR 1118, a Lfa 1 Antagonist, to Decrease Diabetes Induced Retinal Leukostasis and Blood Retinal Barrier Breakdown. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5334.
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One objective of this study was to determine the efficacy of SAR 1118 eye drops in reducing diabetic retinopathy induced leukostasis and blood retinal barrier breakdown. Another objective of this study was to develop a slow release microparticle formulation for SAR1118
Efficacy of 1 and 5% eye drops administered thrice daily over two months was assessed in diabetic Brown Norway rats. FITC-ConA lectin was perfused into anaesthetized rats to label leukocytes. Subsequently, eyes were enucleated and retinal leukocytes were counted in flat mounts. Myeloperoxidase activity in the retina was assessed using a MPO fluorometric detection kit. Blood retinal barrier (BRB) breakdown was studied using FITC-dextran leakage and vitreous to plasma protein ratio. Poly (lactide-co-glycolide) polymer (PLGA) based microparticle formulation was also developed for SAR 1118. Microparticles were assessed for drug loading, particle size, and drug release.
The number of adherent leukocytes decreased significantly by 25 and 55% with 1 and 5% SAR 1118 eye drops, respectively. Similarly, dose dependent decreases were observed in MPO activity, FITC-dextran leakage, and vitreous to plasma protein ratio, with the decreases in these parameters for 5% eye drop treatment being 28, 55, and 32%, respectively. The microparticles exhibited low burst release and sustained the drug release during a four month study.
SAR 1118 is effective in alleviating diabetic retinopathy associated retinal leukostasis as observed by the reduction in leukocyte count and myeloperoxidase enzyme activity. SAR 1118 reduces FITC-dextran leakage and vitreous to plasma protein ratio, which is indicative of an improvement in BRB integrity
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