Serum production against Tityus serrulatus scorpion venom using cross-linked chitosan nanoparticles as immunoadjuvant

Abstract

Several species of scorpions are known to cause accidents which can lead to death, most of them belonging to the genus Tityus. Tityus serrulatus is considered the most dangerous scorpion in South America. In Brazil, T. serrulatus is responsible for serious accidents, including deaths, which occur mainly with children and elderly people. Anti-scorpion sera are routinely produced by various institutions, and suitable technologies have been investigated for encapsulation and release recombinant or native proteins capable of inducing antibody production. In this context, biocompatible and biodegradable polymers, such as chitosan, have been employed for this purpose. This study aimed to obtain a protein release system for the peptides or proteins from T. serrulatus, based on cross-linked chitosan nanoparticles (CN) in order to generate a new model of immunization in animals, and consequently a potentially novel polyclonal serum, namely an anti-T. serrulatus venom. CN were successfully obtained by ionic gelation using the polyanion tripolyphosphate (TPP), which demonstrated a suitable particle size of about 200 nm, with maximum encapsulation efficiency (100%) and enhanced antigen-specific antibody titers of 72%. The serum production data revealed that CN were equipotent to aluminum hydroxide, the traditional adjuvant for immunization. This study demonstrates that chitosan nanoparticles are a promising and safe system for peptide/protein delivery for T. serrulatus scorpion.

Antivenom Production against Bothrops jararaca and Bothrops erythromelas Snake Venoms Using Cross-Linked Chitosan Nanoparticles as an Immunoadjuvant

“…Fourier transform infrared (FT-IR) spectroscopy analyses were used to evaluate the interactions between chitosan and the venom proteins. This evaluation was based on the fact that this interaction leads to frequency shifts or absorption band splitting [ 21 ]. Figure 3 shows the spectra recorded for the CNPs and protein–protein nanoparticles containing distinct snake venoms loaded at a 10% w / w concentration.…”

“…The serums routinely produced are safe and effective for treatment. However, some problems have arisen related to the application of immunoadjuvants for vaccines and sera, such as the toxic potential and collateral effects of these formulations [ 21 , 22 , 23 ]. Aluminium-containing adjuvants are approved by the United States Food and Drug Administration for human use and are widely applied in immunobiological production [ 23 ].…”

“…Hydrophilic nanoparticles have received much attention regarding their ability to deliver therapeutic peptides, proteins, antigens, oligonucleotides, and genes by intravenous, oral, and mucosal administration routes [ 34 , 35 ]. For protein incorporation, the ideal diameter of a nanoparticle should be between 100 and 200 nm [ 21 , 36 , 37 ]. Nanoparticles can potentially circulate for a long time in the body, releasing their loads over multiple hours or days, depending on their properties [ 33 , 38 , 39 ].…”

“…CN has been extensively investigated for carrier and delivery system formulations for therapeutic macrosolutes. Particularly, gene and protein molecule formulations have been explored due to the positive charge of chitosan, which can be easily complexed with negatively charged DNAs and proteins [ 21 , 46 , 47 ]. Chitosan can effectively bind DNA and proteins, protecting these molecules from nuclease and protease degradation, respectively [ 47 ].…”

“…Effective immune responses have been observed when chitosan was used as an immunoadjuvant in vaccines for immunization against Helicobacter pylori [ 48 ], diphtheria [ 49 ], hepatitis B [ 50 ], T. serrulatus venom [ 21 ], and Naja naja oxiana snake venom [ 36 ]; moreover, CN has recently been applied in gene therapy strategies for the control of Aedes aegypti mosquito proliferation [ 43 ].…”