Síntese e caracterização do copolímero PLGA e estudos in vitro de sua degradação e liberação do fármaco atenolol

Abstract

In this present work, the copolymer poly (D,L-lactide-co-glycolide), PLGA, a biomaterial for application in drug delivery systems, was synthesized. The copolymers were synthesized by opening the rings of the cyclic dimers of the D,L-lactide and glycolide monomers. The reactions were performed during 2 hours at 175°C. Different ratios of monomers in the synthesis of PLGA were used: 50/50, 70/30 and 82/18, expressed as the ratio between the mass of D,L-lactide and glycolide, respectively. The latter one was chosen due its greater reproducibility, ease to handle and for being the ratio of monomers that is most applied in drug delivery systems. For the study of in vitro degradation of PLGA 82/18 devices were produced in the form of rod-shaped and the release study of atenolol drug, in addition to rod-shaped, were also produced devices in the form of nanofiber mats (by electrospinning) of PLGA 82/18. Thermogravimetry (TG), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), rheometry, cytotoxicity, ultraviolet-visible spectroscopy (UV-Vis) and scanning electron microscopy (SEM) were used as methods and analysis techniques. The synthesis of PLGA copolymers were performed successfully, and proven by the analysis techniques. The in vitro hydrolytic degradation of PLGA, rod-shaped, showed a marked decrease in 28 days, when in phosphate buffered saline (PBS) solution. The cytotoxicity test, using the MTT reduction technique, showed that the synthesized copolymer PLGA's, lyophilized and processed by electrospinning may not be harmful, because it not caused damage in isolated cells of the body. The atenolol release tests from the PLGA devices, as nanofiber mats, in PBS solution, showed release of 72% of the drug within 24 days of study. The PLGA devices with rod-shaped atenolol showed a slower release in comparison to the mat shaped ones, releasing 8.0% of the initial amount after 30 days in PBS solution. The model used to study the mechanism of release of atenolol from these devices was not adequate to describe the drug release kinetics. The two types of devices presented very different release profiles. By comparing two types of PLGA devices before and after the release study, it was observed that, have undergone the process of hydrolytic degradation in its polymer chains. The studies showed that the synthesized copolymer has potential for application in a modified drug delivery systems.