Use of 2D and co-culture cell models to assess the toxicity of zein nanoparticles loading insect repellents icaridin and geraniol

Author(s)

Germano-Costa, T. ; Bilesky-Jose, N. ; Guilger-Casagrande, M. ; Pasquoto-Stigliani, T. ; Rogerio, CB. ; Abrantes, DC. ; Maruyama, CR. ; Oliveira, JL. ; Fraceto, LF. ; Lima, R.

• Document type: Journal article
• Source: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 216, p. 12-pg., 2022-08-01.

Abstract

After the latest dengue and Zika outbreaks, the fight against mosquito vectors has become an emerging area of research. One tool for this combat is repellents; however, these products are composed of different toxic agents. Botanical compounds with repellent potential are an alternative; however these compounds are highly volatile. Thus, the present study aimed to synthesize zein-based polymeric nanoparticles as an efficient carrier system for the sustained release of the repellents icaridin and geraniol and evaluate the toxicity of these nanorepellents comparing two different cell models. In vitro tests were carried out due to current Brazilian legislation pro-hibiting animal testing for cosmetics (current classification of repellents). The cytotoxicity and genotoxicity of the nanoparticles were evaluated in 2D and co-culture cell models (A549/lung epithelium, HaCaT/keratinocytes, HT-29/intestinal epithelium, and THP-1/peripheral blood monocytes). Cell viability by mitochondrial activity, cell membrane integrity, damage to genetic material, and expression of genes involved in the allergic/inflam-matory system were evaluated. The results of cytotoxicity evaluation showed cell viability above 70% in both cell models. No differences were observed in genotoxicity assessment between cells exposed to nanorepellents and controls. In contrast, gene expression analysis showed increased cytokine expression for the emulsion compounds in 2D cell cultures compared to co-cultures. These findings open perspectives that zein-based nanorepellents have potential applications due to the reduced toxicity observed when the compounds are encapsulated and emerge as an alternative for arbovirus control. In addition, the study demonstrated that depending on the analysis, different results might be observed when comparing 2D and co-culture cell models to evaluate the toxicity of new nanosystems. (AU)

• FAPESP's process: 20/05816-2 - Study of the capping of biogenic nanoparticles and their correlation with toxicity and activity in the control of phytopathogens
• Grantee: Mariana Guilger Casagrande
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/20932-6 - Green synthesis and evaluation of iron nanoparticles based on Trichoderma harzianum for application in agriculture
• Grantee: Natalia Bilesky José
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/14734-0 - Long term repellents containing mixtures of active ingredients with nanoestrutured lipid careers in order to combat the propagation of arboviroses
• Grantee: Daniele Carvalho Abrantes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/18231-4 - Polymeric microparticles as the fungus Trichoderma harzianum carrier system aimed at applications in agriculture
• Grantee: Cintia Rodrigues Maruyama
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/25702-9 - In vitro toxicity evaluation of the carrier systems for development of long-term repellent in 2D, co-culture and 3D models
• Grantee: Tais Germano da Costa
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/02404-5 - Hydrogels containing the geraniol and icaridine repellents encapsulated in zein nanoparticles as an alternative to combat arboviruses
• Grantee: Carolina Barbara Rogerio
• Support Opportunities: Scholarships in Brazil - Scientific Initiation