Desenvolvimento de implantes biodegradáveis constituídos de copolímero dos ácidos lático e glicólico e losartan

Abstract

Glaucoma is the second cause of vision loss around the world and it is mainly developed by elevate intraocular pressure. The glaucoma treatment in the majority of patients starts with drugs, but some of them continue losing vision, which becomes necessary the filtering surgery. The success of the surgery is determinate by the post operative healing process. There are two fibrotic agents such as 5-fluorouracil and mitomycin C which are used to reduce the scars after the surgery. However, these treatments are often associated with serious complications. Losartan has become a promising drug to be used as an adjunct to glaucoma filtering surgery since it presents a potential antiangiogenic and inhibitory fibroblasts proliferation activity. The safety and efficacy of topical and systemic therapies for ocular diseases are limited due to poor ocular drug absorption, the absence of specificity to target tissues, systemic adverse effects and low treatment adherence by patients. The intravitreal injections could overcome these problems however they are associated with many complications. Systems for drug delivery with a prolonged release profile have been developed to overcome these limitations. In this work, biodegradable implants composed of PLGA and losartan were developed and characterized by differential scanning calorimetry, thermogravimetry, infrared spectroscopy and scanning electron microscopy. It was also determined their in vitro release profile, their antiangiogenic activity and their inhibitory fibroblasts proliferation activity. The developed implants show prolonged release profile. It was confirmed the inhibitory fibroblast proliferation activity of the implants although the antiangiogenic activity was only observed with losartan in solution. Thus these implants have the potential for the treatment of undesirable scarring after glaucoma filtering surgery.