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

Investigative Ophthalmology & Visual Science
Aniruddha AmriteUday Kompella

Abstract

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. 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...Continue Reading

Citations

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