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M.G. B. Rego, S.L. Fialho, A. Silva–Cunha, J.A. Cardillo, R.C. Siqueira, R. Jorge; In Vitro Evaluation Of Sustained–release Intravitreal Dexamethasone Implants. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5060.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:To evaluate, in vitro, the pharmacokinetics of a biodegradable device for intravitreal sustained delivery of dexamethasone. Methods:A new biodegradable implant (1 mm in diameter and 4 mm in length) made of poly(D,L–lactide–co–glicolide) 50:50 (PLGA 50:50) and containing 25% dexamethasone (DEX) was developed. The long term in vitro release rate was determined by immersing the device in 2.0ml of PBS (pH, 7.4, 37ºC). After predetermined intervals, the entire volume was sampled and 2.0ml of fresh buffer was added. The amount of DEX into the medium was measured by high–performance liquid chromatography. Results:The developed implant presented as a monolithic system, where the drug is homogeneously dispersed. PLGA matrices degrade by hydrolysis, and breakdown to their constituent monomers, lactic and glycolic acids, which are nontoxics. The degradation of these polymers proceeds faster in the center than at the surface of the device, forming water channels, which connect the surface to the inside of the implant and allow drug diffusion. In the beginning of this in vitro study, the drug deposited on the surface and in the water channels was, probably, released. Next, a slow drug release stage, attributed to diffusion through the initial pores already present and the new channels formed during the polymer degradation process, was observed and the implants presented changes in their initial structures. The devices showed a maximum percent release of 44.5 ± 0.56% in 17 weeks (n = 8). In vivo studies are under development. The correlation between in vitro and in vivo profiles of the implants, that could maintain the drug concentration within the therapeutic range for a long period, would decrease the necessity of repeated intravitreal injections. Conclusions:These results suggest that the intravitreal implant would be a promising system for controlled delivery of DEX to the posterior segment of the eye and an important therapeutic device regarding vitreoretinal diseases.
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