Avaliação biológica de implantes biodegradáveis contendo ciclosporina (A) de administração intravítrea

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 polym ers 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 drug deliver y system due to its satisfactory egradability, biocompatibility and absence ofsignificant toxicity in vivo studies. Aiming the development of a new system to treat posterior uveitis that is not treaty with corticoids therapy, this study has evaluated the viability and safety of an biodegradable implants based on poly (D,Llactidecoglycolide) (PLGA 75:25) and the Cyclosporine A (CyA) previously developed. The validated method applying Mass Espectroscopy detector (MS) High Performance Liquid Cromatography (HPLC) showed to be suitable to quantify the concentrations of CyA in the vitreous on the order of nanograms. The system presented a d rug delivery profile (DDS) where 42,8% of CyA were delivered and 22,8% of matrix mass were lost in eight weeks. From the in vivo delivery study, it was possible to show that the drug delivery was determinate by the first and second drug delivery pathways. The Korsmeyer-Peppas mathematical model analysis demonstrated that the drug delivery occurs mainly due to the drug diffusion from the swelling and porous polymeric matrices. Additionally, it was estimated the CyA permanence period in the vitreous of seventeen weeks once it was founded the CyA half-life of 69,3 days and the CyA elimination constant rate of 3 µg per day, a lower quantity as compare d to the therapeutically CyA doses provide in the systemic administration. The light microscopy analysis showed the eye integrity constituents and the absence of any inflammatory manifestation. In addition, the histology findings confirmed themaintenance of the structure and organization of the retinal tissue when the system is suspended in the vitreous viscous. However, some retinal function alteration was observed by the electrophysiological studies (ERG) once it was detected the B wave suppression in the eye that received the implants containing the CyA. From the CyA intravitreal injection of in a highest therapeutically dose, it was possible to classify this toxicity as a transitory behavior once it was reverted twelve days after the totally drug elim ination.