Subconjunctival nano- and microparticles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting VEGF expression.

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Kompella UB, Bandi N, Ayalasomayajula SP

Subconjunctival nano- and microparticles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting VEGF expression.

Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1192-201.

PubMed ID

12601049 [ View in PubMed

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Abstract

PURPOSE: The purpose of this study was to determine whether budesonide inhibits expression of vascular endothelial growth factor (VEGF) in a retinal pigment epithelial cell line (ARPE-19) and to determine whether subconjunctivally administered budesonide nano- and microparticles sustain retinal drug levels. METHODS: The effect of budesonide (100 pM to 10 microM) on VEGF secretion, expression of VEGF mRNA, and cytotoxicity were determined in ARPE-19 cells by ELISA, RT-PCR, and a cell-viability assay, respectively. To determine the involvement of glucocorticoid receptor in the observed effects of budesonide, secretion and mRNA expression studies were also performed in the presence of a glucocorticoid receptor antagonist (RU486). DL-Polylactide (PLA) nano- and microparticles containing budesonide were prepared by a solvent evaporation technique, and the particles were characterized for size, morphology, encapsulation efficiency, and in vitro release. Budesonide-PLA nano- and microparticles were administered subconjunctivally to one eye of Sprague-Dawley rats and drug levels in the retina, vitreous, lens, and cornea of both eyes were determined at the end of 1, 7, and 14 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. RU486 treatment prevented budesonide-mediated inhibition of VEGF secretion and VEGF mRNA expression. Budesonide-PLA nano- (345 nm) and microparticles (3.6 microm), with an encapsulation efficiency of 65% and 99%, respectively, sustained budesonide release in vitro. After subconjunctival administration, both budesonide-PLA nano- and microparticles produced sustained budesonide levels in the retina and other ocular tissues. CONCLUSIONS: Budesonide is capable of inhibiting VEGF expression through glucocorticoid receptor activity. Subconjunctivally administered budesonide-PLA nano- and microparticles sustain retinal drug delivery.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Budesonide	Glucocorticoid receptor	Protein	Humans	Yes	Agonist	Details