In vivo release and retinal safety of intravitreal implants of thalidomide in rabbit eyes and antiangiogenic effect on the chorioallantoic membrane Silvia L. Fialho1, Pedro A. F. Souza1, Gustavo O. Fulgeˆncio2, Murilo M. O. Miranda3, Bruno G. Pereira1, Antonio Haddad4, Andre ́ Messias3, Rodrigo Jorge3, and Armando Silva-Cunha2 Abstract Purpose: To evaluate the in vivo release, retinal safety and antiangiogenic effect of a thalidomide-loaded poly-lactide-co-glycolide intravitreal implant. Methods: New Zealand white rabbits, divided into two groups, I and II, received an intravitreal implant containing or not thalidomide, respectively (n1⁄412). Intravitreal drug levels were determined during a six-week study period. The potential for toxicity associated with the implants was evaluated by electroretinography and light microscopy (n1⁄48). Twelve chorio- allantoic membranes (CAMs) from chicken eggs were incubated with thalidomide dispersion, implants containing or not thalidomide and vitreous samples and analyzed after two days regarding the percentage of vessels regression. Results: Intravitreal concentrations of thalidomide (ng/ml) were 690.21 +- 177.95, 372.51 +- 185.56, 240.59 +- 133.48, 327.54 +- 169.71, 294.26 +- 142.41 and 465.18 +- 157.51 at 1, 2, 3, 4, 5 and 6 weeks, respectively, after implantation in group I rabbits. No drug was detected in group II samples. Electroretinography and histological evaluations did not show any sign of retina toxicity. There was significant regression of vessels in CAM incubated with thalidomide dispersion, thalidomide-loaded implants and vitreous samples from group I when compared to control. Conclusion: The intravitreal implants delivered safe doses of thalidomide that were also effective to induce vessels regression in CAMs. Keywords Biomaterials, controlled release, drug delivery systems, ophthalmic drug delivery, PLGA, toxicity
