Cationic PLGA Nanoparticle Formulations as Biocompatible Immunoadjuvant for Serum Production and Immune Response against Bothrops jararaca Venom

Toxins (Basel). 2022 Dec 19;14(12):888. doi: 10.3390/toxins14120888.

Abstract

Snakebite envenoming represents a worldwide public health issue. Suitable technologies have been investigated for encapsulated recombinant or native proteins capable of inducing an effective and long-lasting adaptive immune response. Nanoparticles are colloidal dispersions that have been used as drug delivery systems for bioactive biological compounds. Venom-loaded nanoparticles modulate the protein release and activate the immune response to produce specific antibodies. In this study, biocompatible cationic nanoparticles with Bothrops jararaca venom were prepared to be used as a novel immunoadjuvant that shows a similar or improved immune response in antibody production when compared to a conventional immunoadjuvant (aluminum hydroxide). We prepared stable, small-sized and spherical particles with high Bothrops jararaca venom protein association efficiency. The high protein loading efficiency, electrophoresis, and zeta potential results demonstrated that Bothrops jararaca venom is adsorbed on the particle surface, which remained as a stable colloidal dispersion over 6 weeks. The slow protein release occurred and followed parabolic diffusion release kinetics. The in vivo studies demonstrated that venom-loaded nanoparticles were able to produce an immune response similar to that of aluminum hydroxide. The cationic nanoparticles (CNp) as carriers of bioactive molecules, were successfully developed and demonstrated to be a promising immunoadjuvant.

Keywords: Bothrops jararaca; PLGA nanoparticles; immunoadjuvants; nanobiotechnology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Aluminum Hydroxide
  • Animals
  • Bothrops* / metabolism
  • Crotalid Venoms* / metabolism
  • Immunity
  • Nanoparticles*
  • Proteins / metabolism

Substances

  • Crotalid Venoms
  • Adjuvants, Immunologic
  • Aluminum Hydroxide
  • Proteins

Grants and funding

This research was funded by Brazilian National Council for Scientific and Technological Development (CNPq) in financial support (grant numbers: 308382/2017-0, 436051/2018-4, 311209/2020-3), and funded in part by the “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Brasil (CAPES)” Finance Code 001.