Sistemas biodegradáveis de administração intra-ocular contendociclosporina (a) para tratamento de uveíte posterior

Abstract

The treatment of posterior ocular disease is limited once the conventional forms of drug administration fail to provide therapeutic levels drug to the vitreous, retina and choroids. The biodegradable polymers intraocular implants are able to release drugs directly to the vitreous and are able to maintain long-term vitreous concentration of drugs in therapeutic range. The poly (D,Llactidecoglycolide) is a classic example amongst the synthetic polymers and well applied as drugdelivery system due to its satisfactory degradability, biocompatibility and absence of significant toxicity accessed by in vivo studies. In this study, two novel different intraocular implants based on poly (D,Llactidecoglycolide) (PLGA 75:25) and the Cyclosporine A (CyA) immunosuppressive have been obtained from two different systems: lyophilized mixture and CyA-loaded microspheres. We havesuccessfully characterized the system with four different techniques and explained to some extent the preliminary long-term in vitro release profile. The HPLC validation results showed to be suitable to quantify the concentrations of CyA and the implants were successfully obtained by both proposed techniques. The TG curves proved the stability of the samples between temperatures of 100 - 120ºC. The materials crystalinities were evaluated by RXD diffraction wich showed anamorphous state of the polymer and CsA semi-crystalline state. Bisade that, the technique has shown the great amorphous state of the samples containing the drug and the polymer. DSC and FTIR have shown the absence of some detectable physical and chemical interaction between drug and polymer. The CyA preliminary release profile consisted by monophasic profile, wich the drug delivery occurs mainly due to the drug diffusion from the sweeling polymeric matrices. The diferrent and higher CyA release associated with samples of CyA-loaded microsphere implants was probably caused by the distinct drug distribution andheterogeneous morphological aspect from those lyophilized mixture implants, which have presented a slow CyA release and homogeneous surfaces. In summary, the delivery systems developed and fully characterized in the present work can be applied, in the future, for the treatment of various types of posterior uveitis manifestation.