Abstract
Purpose: :
Retinal delivery of budesonide, a corticosteroid capable of reducing VEGF expression in the retinal cells, can be sustained using subconjunctivally administered drug encapsulating poly(lactide) (PLA) microparticles. The purpose of this study was to determine whether subconjunctival budesonide and budesonide–PLA suspensions do not induce IOP elevation, cataracts, and other complications in a rabbit model.
Methods: :
Suspension of budesonide or budesonide–PLA microparticles (15 mg drug; 0.5 ml volume) was injected subconjunctivally into one eye of New Zealand white male rabbits and the other eye received the vehicle or placebo PLA microparticles. The eyes were assessed for intraocular pressure, lens opacity, and fundus abnormalities. The parameters were measured one day before (baseline) dosing and repeated at 3 days after the injections, and then every week for 2 months. Blood samples were collected at the time of sacrifice and analyzed for complete blood chemistry. The rabbits were sacrificed at the end of 4 weeks and the eyes were enucleated and fixed for histological assessment of the retina and the site of injection.
Results: :
The IOPs did not differ from controls throughout the study. No lens opacities or fundus abnormalities were observed in any of the groups. The mean values of blood chemistry parameters were within the normal range of expected values, although glucose levels were higher in some rabbits. No abnormalities were found in the fundus photos. Particles were found at the site of injection but no abnormalities were seen in the surrounding tissue. The retina appeared normal.
Conclusions: :
Subconjunctival budesonide and budesonide–PLA microparticle suspensions do not elevate IOP, induce lens opacities, or alter retinal architecture. Thus, budesonide drug delivery systems are of potential value in treating inflammatory and neovascular disorders of the eye.
Keywords: drug toxicity/drug effects • retina • conjunctiva