Desenvolvimento, caracterização e atividade anticoagulante de nanopartículas de PLGA/PVA contendo pectina sulfatada extraída do melão japonês (Cucumis melo var. Acidulus)

Abstract

For the control and prevention of coagulation disorders, numerous polysaccharides can be used, with unfractionated heparin (UFH) and fractionated heparin (HF) being the most promi-nent. As these glycosaminoglycans have limitations of use, many studies have been conducted in order to identify substances with similar effects. In this context, the literature states that sulfated polysaccharides are polymers with anticoagulant potential. In order to find an alterna- tive to heparins, tests on the anticoagulant activity of three isolated and chemically sulfated natural polysaccharides were carried out: galactomannans extracted from Carolina [Adenan- thera pavonina (L.)] and Flamboyant [ Delonyx regia (Boger ex Hook.)], And pectin extract- ed from Japanese melon (Cucumis melo var. Acidulus). Of these, sulfated pectin (PS) was selected because it has the most promising anticoagulant activity. Complementing the in vitro assays, this polysaccharide was subjected to the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) tests, where it was possible to verify linear and dose-dependent APTT results. Considering that polymeric nanoparticles play an im- portant role in future therapies, this study also proposed the preparation and characterization of Poly D, L-Lactide-co-glycolide (PLGA) nanoparticles containing sulfated pectin, through the double emulsion method with solvent evaporation, using polyvinyl alcohol (PVA) as a surfactant. Subsequently, the nanoparticles obtained were properly characterized in terms of their physical-chemical characteristics, and analyzed for stability, release, morphology, and rheological behavior. Scanning electron microscopy (SEM) exhibited spherical and homoge- neous nanoparticles. Differential Scanning Calorimetry (DSC) and Thermogravimetry (TG) revealed compatibility between the system components. The nanoparticles produced obtained an average diameter of 301.03 nm, zeta potential -16.63 mV, and IPD 0.18. The encapsulation efficiency (EE) was 76.31%. Within 5 days, 49% of PS was released. The rheological behav- ior of sulfated pectin formulations was similar to that of commercial heparin, suggesting good syringability. The results of in vitro tests for the anticoagulant activity of sulfated pectin con- firmed the slow and effective release for controlled release systems. In view of the results presented, it was possible to verify that sulfated pectin has dose-dependent anticoagulant po- tential, and its nanoencapsulated form is stable and represents a proposal for controlled anti- coagulant therapy in a possible subcutaneous administration route.