Obtenção e avaliação do potencial imunoadjuvante de nanopartículas de quitosana na produção de antissonoros contra venenos de serpentes e escorpiões

Abstract

Accidents with venomous animals represent a serious public health problem in many countries of the world, with emphasis to snake and scorpion accidents. In Brazil, Bothrops snakes are the most clinically relevant. Regarding scorpions, the genus Tityus includes the species of higher medical importance. Treatment for envenomation consists mainly in the administration of antivenom sera. Vaccines using pure antigens in alternative administration routes require the use of potent adjuvants and an effective antigen delivery system. Nanosystems are being investigated as delivery systems for therapeutic macromolecules. Chitosan, due to its properties, has been extensively investigated in nanocarriers formulations, particularly for genes and proteins. This study aimed to obtain chitosan nanoparticles (CNP) based on ionic gelation for the delivery of therapeutic proteins/peptides used in immunotherapy, as well as to evaluate the immunoadjuvant potential of these nanoparticles in the production of antivenom serums. CNP were obtained by ionic gelation, with an average size of 160 nm. Physicochemical characterization and evaluation of the release profile demonstrated that it is a modified release system. The stability of different systems was evaluated for 7 weeks, observing a greater stability of the systems associated with venoms. Experimental animals were immunized subcutaneously for 6 weeks with 100 uL snake venoms at different concentrations (5.0 or 10.0%), either encapsulated in CNP or associated with aluminum hydroxide (AH). The results demonstrate that the antibody titers observed for animals vaccinated with the studied nanosystems were equivalent or higher than those observed for animals vaccinated with HA. Further advantages of the nanosystems were to be less inflammatory, and to require smaller amounts of antigen to be administered, because it is a modified-release system, with potential application in anti-venom serum therapy.