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U Kompella, SP Ayalasomayajula; Sustained Delivery of Budesonide to the Posterior and Anterior Segments of the Eye Using Subconjunctivally Administered Biodegradable Nanoparticles . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2300.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To determine whether budesonide inhibits VEGF expression in cultured retinal pigment epithelial cells (ARPE-19) and to determine whether subconjunctivally administered budesonide nanoparticles will sustain drug levels in the eye. Methods:The effect of budesonide (100 pM to 10 µM) on VEGF secretion, VEGF mRNA expression, and cytotoxicity was determined in ARPE-19 cells using ELISA, RTPCR, and MTT assay, respectively. Also, the effect of RU-486 (0.1, 1, and 10 µM) treatment on the ability of budesonide to induce changes in VEGF expression in ARPE-19 cells was determined. Using solvent-evaporation technique, budesonide-D-L-poly (lactic acid)(PLA) nanoparticles were prepared. The particle size and charge were determined using Zeta-plus particle size analyzer. The drug release profile from nanoparticles was determined using dialysis membrane bags and budesonide was analyzed using a HPLC method. Budesonide-PLA nanoparticles (50 µg budesonide) were administered subconjunctivally to each eye of Sprague Dawley rats and drug levels in the retina, vitreous, lens, and cornea were determined at the end of 7 days. Results:At concentrations devoid of cytotoxicity, budesonide inhibited VEGF secretion as well as mRNA expression in ARPE-19 cells in a dose-dependent manner with the maximum inhibition occurring at 100 nM. RU-486 (1 and 10 µM) treatment prevented budesonide-mediated inhibition of VEGF expression. Solvent-evaporation technique yielded budesonide-PLA nanoparticles of size 284 ± 25 nm with a drug loading of 17% (65% encapsulation efficiency). PLA nanoparticles sustained budesonide release with 50% of the loaded drug released at the end of 7 days. The budesonide levels at the end of 7 days in retina, vitreous, and cornrea were 0.6 ± 0.06, 0.06 ± 0.004, and 3.7 ± 0.6 ng/mg tissue, respectively. Budesonide was below detection limit (0.5 ng) in the lens extract. Conclusion:Budesonide inhibited VEGF secretion and VEGF mRNA expression in ARPE-19 cells via its glucocorticoid receptor activity. Subconjunctival administration of budesonide-PLA nanoparticles sustained drug delivery to the posterior segment as well as anterior segment of the eye.
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