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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Single periocular injection of celecoxib-PLGA microparticles inhibits diabetes-induced elevations in retinal PGE2, VEGF, and vascular leakage.

PURPOSE: To determine whether celecoxib inhibits VEGF secretion from ARPE-19 cells and to investigate further the safety and effectiveness of periocular celecoxib-poly (lactide-co-glycolide; PLGA) microparticles in inhibiting elevations in retinal PGE(2), VEGF, and blood-tissue barrier leakage at the end of 60 days in a streptozotocin diabetic rat model. METHODS: VEGF mRNA and protein expression in ARPE-19 cells was evaluated in the presence of 0 to 10 microM celecoxib, and cytotoxicity of celecoxib on ARPE-19 and RF6A cells was evaluated over a 0- to 100-microM concentration range. Celecoxib-PLGA microparticles were prepared by a modified solvent evaporation technique, sterilized by 25 kGy of gamma-irradiation, and characterized for size, zeta potential, drug loading, and in vitro release. Normal and streptozotocin-diabetic male Sprague-Dawley rats were divided into five groups: normal, diabetic, diabetic+placebo, normal+celecoxib, and diabetic+celecoxib. Phosphate-buffered saline (PBS) containing celecoxib-PLGA microparticles, placebo PLGA microparticles, or plain PBS in one eye was injected into the posterior subconjunctival (periocular) space in rats under anesthesia. Sixty days after administration, the animals were killed, and retinal PGE2 secretion, VEGF protein, and blood-retinal barrier leakage were estimated. Blood cell counts, blood chemistry and histology were used to assess the safety of the microparticulate system. RESULTS: Celecoxib (up to 25 microM) did not cause significant cytotoxicity in ARPE-19 or RF6A cells. Nanomolar concentrations of celecoxib reduced VEGF mRNA and VEGF protein secretion. Celecoxib-PLGA microparticles (diameter: 1140 +/- 15 nm), containing 14.93% +/- 0.21% of celecoxib sustained in vitro drug release and in vivo drug levels in the retina for 60 days. Diabetes elevated PGE2 secretion, VEGF protein, the vitreous-plasma protein ratio, and blood-retinal barrier leakage by 3-, 1.7-, 3.1-, and 2.7-fold, and celecoxib-PLGA microparticles significantly reduced these elevations by 40%, 50%, 40%, and 50%, respectively. Neither the placebo-treated eyes nor the contralateral eyes in celecoxib-PLGA microparticle-treated rats showed significant effects. Celecoxib-PLGA or placebo-PLGA particles had no effect on the body weight or blood sugar level of rats. The celecoxib-PLGA microparticles did not cause any changes in blood cell counts or chemistry and caused no histopathological damage to the retina or periocular tissues. CONCLUSIONS: Nanomolar concentrations of celecoxib can inhibit VEGF mRNA and protein expression from ARPE-19 cells. Periocular celecoxib microparticles are useful sustained drug delivery systems for inhibiting diabetes-induced elevations in PGE2, VEGF, and blood-retinal barrier leakage. The periocular celecoxib-PLGA microparticles are safe and do not cause any damage to the retina.[1]


  1. Single periocular injection of celecoxib-PLGA microparticles inhibits diabetes-induced elevations in retinal PGE2, VEGF, and vascular leakage. Amrite, A.C., Ayalasomayajula, S.P., Cheruvu, N.P., Kompella, U.B. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
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