Desenvolvimento e caracterização de sistemas biodegradáveis de liberação de ácido micofenólico para administraçâo intraocular

Abstract

Mycophenolic acid (MPA) is an immunosuppressive agent widely used in the treatment of organ transplant rejection. In some preliminary studies, MPA has been shown to inhibit experimental autoimmune posterior uveitis in rats, and its use in human posterior inflammatory eye disease has been already described. Treatment of inflammatory eye diseases in the posterior chamber is a challenge due to the anatomy of the eye, which has natural barriers that make the drug access more difficult. Thus, the bioavailability of drugs inside the eye is very low, and a successful therapy may be directly related with the drug release profile in this target. To solve this problem, a biodegradable polymeric device in the form of eye implant for the controlled release of MPA directly into the eye was developed. The implant has 6 mm of length and 0.5 mm of diameter, a dosage of 160 g of MPA, and a polymeric matrix constituted of poly lactic acid and glycolic (PLGA). To characterize the new device, an analytic method of ultra performance liquid chromatography (UPLC) was developed and applied on the MPA assay in the new device. The method has a quantitation limit of 0.3 mg / mL and a run time of 1.5 minute. This same method was used for quantification of MPA released by the device on an in vitro release study in which it was possible to verify the drug release over a period of 15 weeks. To quantify the drug released inside the eye and study the behavior of the device in vivo, a bioanalytical method was developed. The implantable device was able to deliver and control the liberation of approximately 10µg of MPA inside rabbit eyes through 40 days.