Nanopartículas poliméricas biodegradáveis de poli (ácido láctico-co-glicólico) funcionalizadas para incorporação de peçonha de Bothrops jararaca

Abstract

Snake-envenoming represents a worldwide public health issue. The search for new immunoadjuvants and vaccines expands the therapeutics alternatives and improves antivenoms sera. Nanotechnology is associated to antivenom serum improvement once venom-loaded nanoparticles modulate the protein release and activating immune response to produce specific antibodies. Polymeric nanoparticles are colloidal dispersions with particle size between 1-1000 nm which have been used as drug delivery systems for bioactive macromolecules. The aim of this study is obtain and characterize biodegradable cationic nanoparticles to proteins loading. The sub 200 nm poly (lactic-co-glycolic acid) (PLGA) nanoparticles were produced and functionalized with hyper-branched polyethylenimine (PEI) using the nanoprecipitation technique. The parameters assessed by dynamic light scattering, zeta potential measurements and morphology were monitored to establish a suitable formulation. Small-sized (100– 200 nm) and spherical particles with protein association efficiency of about 100% were reached. The high protein loading efficiency, electrophoresis and zeta potential results demonstrated that Bothrops jararaca venom were adsorbed on particle surface, which remained as a stable colloidal dispersion (over 6 weeks). A slow release protein profile was observed admitting the release kinetics by parabolic diffusion. The in vivo studies showed immunoadjuvant ability of the nanoparticles, similar to that found to aluminum hydroxide. Thus, the cationic nanoparticles as carrier to bioactive molecules was successfully developed and demonstrated to promising immunoadjuvant and a novel nanocarrier for protein or nucleic acids release.