Desenvolvimento de sistemas de liberação de fármacos de aplicação supracoroidal constituídos de poliuretano para o tratamento de inflamações oculares.

Abstract

The treatment of diseases of the posterior segment of the eye is limited once the conventional forms of drug administration fail to provide therapeutic levels drug to the vitreous, retina and choroids. Intravitreal injections have been used to deliver drugs to the posterior segment of the eye, but it is an invasive technique with a lot of potential risks. The biodegradable implants are able to release drugs directly to the vitreous and to maintain long-term vitreous concentration of drugs in therapeutic range. The polyurethanes (PUD) are biodegradables synthetic polymers widely used in drug delivery systems due to their biocompatibility, adjustable mechanical and physics properties according to the necessity and synthesis free of organic solvents, reducing toxicity. In this work, PUD (polyurethane aqueous dispersion) films and dexamethasone (DX), one of the most widely used corticosteroids in the treatment of uveítes, were developed and characterized by Fourier transform infrared spectroscopy (FTIR) and the long-term in vitro release profile was determined. Biocompatibility and effectiveness of the system were assessed in an animal model of acute anterior uveítes EIU (endotoxin-induced uveítes). The results show that it was possible to obtain PUD films containing different concentrations of DX, by reproducible methods that provide drug in dispersed and active form in the polymeric matrix. The systems were successfully implanted in suprachoroidal space, showing biocompatibility and safety at in vivo tests. PUD biodegradable film containing DX was able to deliver effective doses of the drug in ocular tissues, inhibiting the characteristic inflammatory response of anterior uveítes by downregulating the expression of pro-inflammatory factors and increasing expression of antiinflammatory factors, while reducing the number of inflammatory cells and the monocytes/microglial cells activation, becoming a promising system for the treatment of ocular inflammatory diseases.