Ácido corosólico na oftalmologia: avaliação da atividade antiangiogênica, segurança e toxicidade ocular, desenvolvimento e caracterização de implante biodegradável de liberação prolongada

• Ano de defesa: 2018
• Autor(a) principal: Cibele Rodrigues Toledo
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Ácido corosólico; Plga; Angiogênese; Implantes biodegradáveis; Neovascularização da retina; Implante intravítreo; Neovascularização; Toxicidade; Tratamento oftalmológico; Retina Vasos sanguíneos
• Link de acesso: http://hdl.handle.net/1843/BUOS-B4WMMY

Angiogenesis occurs in pathological conditions as an attempt to repair tissue damage through the local formation of blood vessels. However, in proliferative retinopathies, neovascularization brings effects that impair visual function. In the control of the ocular neovascularization process, the intravitreal administration of drugs with antiangiogenic properties is still preferred among the available therapeutic schemes, although frequent injections are necessary. Therefore, the search for new substances that can be used in the treatment of these diseases, as well as the development of sustained release systems, has been of great interest. Within this scenario, the objective of this study was to evaluate the antiangiogenic activity and the safety of intravitreal administration of corosolic acid (AC), and to develop sustained release systems aiming at the treatment of diseases causing retinal neovascularization. The cytotoxicity of AC in the retinal-pigmented epithelium cell line (ARPE-19) was determined for a period of 48 hours by the colorimetric method of sulforhodamine B, and no toxicity was observed at concentrations below 35,5 mol/L. The antiangiogenic activity of AC was evaluated in an in vivo model of the chicken embryo chorioallantoic membrane (CAM) and it was observed that concentrations between 5 and 25 mol/L were able to inhibit neovascularization, revealing AC as a promising therapeutic option for the treatment of pathological angiogenesis. Intravitreal administration of AC was also performed in eyes of Wistar rats, and retinal toxicity signs for a period of 15 days were not checked by electroretinography and histological evaluation. Thus, AC at concentrations below 25 mol/L was considered safe for ophthalmic use. To overcome the drawbacks of frequent intravitreal administration, a biodegradable sustained release system has been developed for carrying AC. Using the hot molding technique, 50:50 PLGA implants containing 11% AC were prepared. An analytical method by high performance liquid chromatography was developed and validated for quantification of AC in the systems. The devices were characterized by infrared spectroscopy, thermal analysis and scanning electron microscopy, and it was not verified any incompatibilities and/or interactions between the PLGA 50:50 polymer and AC. In vitro release studies were conducted and the percentage of released AC was determined over 8 weeks, demonstrating the suitability of the system for a continued release of AC over a period of 60 days. The biocompatibility of the implants was confirmed by the CAM biological assay. Therefore, from the obtained results, biodegradable implants containing AC have been shown as a promising alternative for the treatment of diseases causing retinal neovascularization.