DEVELOPMENT OF NANOSYSTEMS FOR EXPERIMENTAL IMMUNIZATION APPLIED TO VISCERAL LEISHMANIASIS
PLA nanoparticles; polyethylenimine; Leishmania infantum; neglected tropical diseases.
Visceral leishmaniasis is the most severe and lethal form of the disease and is considered one of the most important neglected tropical illnesses. Current treatments exhibit high toxicity and limited efficacy, reinforcing the need for safer and more effective alternatives. In this context, the present study aimed to develop and characterize poly(lactic acid) (PLA) nanosystems functionalized with polyethyleneimine (PEI) and incorporated with total antigens of Leishmania infantum, evaluating their potential as an immunotherapeutic platform. The nanoparticles were obtained by nanoprecipitation and characterized in terms of size, zeta potential, morphology, and physicochemical stability over a 30-day period. Cell viability assays were performed using fibroblast (3T3) and macrophage (RAW 264.7) cell lines, and the humoral immune response was investigated in BALB/c mice immunized and monitored by ELISA. The results demonstrated that the formulations displayed nanometric size (209–297 nm), spherical shape, appropriate colloidal stability, and incorporation efficiency of up to 98.8% in cationic systems. PLA nanoparticles exhibited low cytotoxicity, whereas PEI-functionalized systems showed concentrationdependent toxicity, which was attenuated by the presence of total L. infantum antigens. Immunization with the nanosystems induced a sustained total IgG humoral response, with predominance of IgG2b and IgG3 subclasses, a profile associated with a Th1-type response, which is more effective against intracellular infections. Notably, the nanosystems promoted favorable immunological modulation, enabling controlled antigen release and inducing a more balanced immune response compared with conventional adjuvants. In conclusion, the nanoparticles developed in this study represent a promising strategy for the immunotherapy of visceral leishmaniasis, combining stability, biocompatibility, and the ability to direct the immune response toward a protective profile.