Avaliação da toxicidade aguda de nanopartículas híbridas lipídicas poliméricas contendo doxorrubicina e succinato de tocoferila.

Abstract

The use of hybrid nanoparticles has become increasingly attractive for drug encapsulation, as these systems combine the advantages of both lipid-based and polymer-based systems. Doxorubicin, a potent antineoplastic agent, has significant therapeutic effects but its use is limited due to the adverse effects associated with treatment, particularly cardiotoxicity. In this context, encapsulating doxorubicin in nanoparticles is an appealing approach as it enhances its therapeutic action while reduces toxicity in healthy cells. Alpha-tocopheryl succinate, a hydrophobic and biodegradable ester derived from vitamin E, also exhibits antitumor properties, making it a valuable adjuvant in treatment. Additionally, its physicochemical characteristics allows the formation of an ionic pair with doxorubicin, which is crucial for successful encapsulation. In this study, the acute toxicity of hybrid lipid-polymeric nanoparticles containing doxorubicin and alpha-tocopheryl succinate (LPNP-DOX-ST) was evaluated in an experimental model. The hybrid lipid-polymeric nanoparticles were prepared using the emulsification/solvent evaporation method and characterized in terms of physicochemical parameters and hemocompatibility. For the toxicity study, healthy mice were treated with either doxorubicin or LPNP-DOX-ST in a single intravenous dose and observed for 7 and 14 days. The animals were euthanized, and blood and organs were collected for hematological, biochemical, and histopathological analyses. Results showed particles with an average diameter of around 140 nm, a polydispersity index of less than 0.3, a zeta potential of approximately -38.0 mV, and an encapsulation efficiency near 100% (99.69±0.05). The formulation was found to be hemocompatible at doses equivalent to 20 mg/kg of DOX. A significant reduction in animal mortality was observed in the group treated with LPNP-DOX-ST compared to the group that received the same dose of free DOX. Additionally, a significant decrease in renal, hepatic, and cardiac toxicity was observed in animals treated with LPNP-DOX-ST. These results suggest that the nanosystem holds promising potential as a therapeutic alternative, as it is capable of reducing systemic toxicity, providing a safer and more effective treatment.