Desenvolvimento de sistemas poliméricos de implantação intraocular contendo tacrolimus para o tratamento de uveítes crônicas

Abstract

Uveitis is responsible for 3-15% of all blindness causes in the world since intraocular inflammation and related complications cause severe vision loss. The treatment of this disease, when it reaches the posterior segment of the eye, has been a problem due to the difficulty of drug access to its target. FK506 (tacrolimus) is an immunosuppressive agent with demonstrated efficacy in treating uveitis; however its systemic administration is associated with significant problems. The biodegradable implants are becoming promising alternatives as delivery systems for intraocular drug delivery as they can release the drug at the site of action for a long period of time. Therefore, the objective of this study was the development and characterization of PLGA (Poly-lactide co-glycolide acid) - based implants for FK506 delivery to the treatment of chronic uveitis. The implants were prepared by hot molding of a lyophilized mixture containing 90% of PLGA (75:25) and 10% of FK506. In the characterization and evaluation of systems, were employed thermal analysis (DSC and TGA), FTIR and SEM. Additionally, in vitro and in vivo release studies, were performed. It was also developed and validated an analytical method forquantification of FK506 present in the devices using HPLC. With the results obtained in the characterization studies, we observed stability of raw materials at the temperature used in the process of devices production and there was no incompatibility between the drug and the polymer. The photomicrographs of implants,obtained by SEM, showed a smooth and uniform surface. However, during the release study the surface became porous and irregular due to the output of the drug by diffusion. The in vitro and in vivo release profiles showed, respectively, a release of 58,20% and 99,97% in 42 days. It was not observed any sign of clinical alterations in the eyes of the rabbits that received the implants.