EVALUATION OF THE ANTIMICROBIAL AND LARVICIDIC POTENTIAL OF THE SNAKE VENOM Crotalus durissus cascavella _LOADED CROSS-LINKED CHITOSAN NANOPARTICLES
Antibacterial; Antifungal; Antiparasitic; Biocompatibility; Larvicidal; Snake venom. Chitosan nanoparticles.
Antimicrobial resistance (AMR) represents a threat to the global population and may be responsible for the emergence and re-emergence of several infectious diseases. Infections caused by multidrug-resistant pathogens present high morbidity and mortality, which has led to an incessant search for new therapeutic alternatives. The South American rattlesnake (Crotalus durissus) contains in its venom several biologically active proteins with important pharmacological action, which can be a valuable tool in the research of new drugs. In order to ensure better use of biologically active molecules, polymeric nanocarriers have been investigated as delivery systems for macromolecules. Chitosan, due to its favorable properties, has been extensively studied in nanocarrier formulations, particularly for proteins and peptides. With this focus, the present study used chitosan nanoparticles (NPQ) as a sustained release system for the Crotalus durissus cascavella venom snake in concentrations of 0.5 and 1.0%, as well as evaluated its biocompatibility and antibacterial, antifungal, antiparasitic and larvicidal potential. The nanoparticles were successfully obtained by the ionic gelation technique. Biocompatibility was evaluated in normal cell lines (Vero E6, and NIH/3T3) and human erythrocytes, demonstrating that in the tested concentrations there was no evidence of hemolytic nor cytotoxic effects. Through the minimum inhibitory concentration test, our results demonstrate the nanoparticles ability to inhibit standard gram-positive and gram-negative bacteria and multi-resistant clinical isolates, in addition to inhibit different species of the genus Candida. In antiparasitic tests, crude venom and the nanoparticles associated with the venom demonstrated cytotoxicity in the epimastigote and trypomastigote forms of Trypanosoma cruzi, presenting as main mechanism of action late apoptosis and low levels of mitochondrial damage. The leishmanicidal effect was mainly evidenced by NPQ associated with venom, reaching almost 100% inhibition by NPQ with venom incorporated at 1.0%. Through the larvicide test it was demonstrated that NPQ without and associated with the venom also demonstrated a promising effect against Aedes aegypti larvae. That way, this study demonstrated the multifunctional potential of chitosan nanoparticles associated or not with venom, as well as crude C.d. cascavella venom, which can be used as a prototype to obtain new drugs with biotechnological application.