A multiparametric and orthogonal approach indicates low toxicity for zein nanoparticles in a repellent formulation.

The incidence of viruses such as Zika, Dengue, and Chikungunya affects human health worldwide, and insect repellents are recommended for individual protection. Formulations incorporating nanotechnology should be carefully assessed for toxicity, particularly regarding the security levels established for human health and the environment. This study evaluates the cytotoxicity of a repellent formulation containing zein nanoparticles (NP) loading geraniol (Ger) and icaridin (Ica) in three cell lines: NIH/3T3, HaCaT, and SIRC. To address formulation hazards, IC50 values were determined by MTT and Calcein-AM assays. In both NIH/3T3 and HaCaT, the IC50 values for NP + Ger + Ica formulation were around 0.2%. For risk assessment, cell viability was also determined after a single exposure and repeated exposure to the formulation. No evidence of cytotoxicity was observed for NP + Ger + Ica formulation-treated cells. The risk assessment for eye damage revealed cytotoxicity in SIRC cells when exposed to a 5% concentration, which may be attributed to ocular geraniol toxicity, because zein nanoparticles alone did not exhibit any signs of toxicity. Cell internalization indicated low uptake in NIH/3T3 and HaCaT cells. Phenotypic profiling resulted in similar phenotypes for untreated cells and cells exposed to NP + Ger + Ica formulation. The toxicological profile outlined by the multiparametric and orthogonal approach suggests that the NP + Ger + Ica formulation poses no significant risk to the topical application under the tested conditions. Adopting an orthogonal approach brings robustness to our findings.

Repellent active ingredients encapsulated in polymeric nanoparticles: potential alternative formulations to control arboviruses.

Dengue, yellow fever, Chinkungunya, Zika virus, and West Nile fever have infected millions and killed a considerable number of humans since their emergence. These arboviruses are transmitted by mosquito bites and topical chemical repellents are the most commonly used method to protect against vector arthropod species. This study aimed to develop a new generation of repellent formulations to promote improved arboviruses transmission control. A repellent system based on polycaprolactone (PCL)-polymeric nanoparticles was developed for the dual encapsulation of IR3535 and geraniol and further incorporation into a thermosensitive hydrogel. The physicochemical and morphological parameters of the prepared formulations were evaluated by dynamic light scattering (DLS), nano tracking analysis (NTA), atomic force microscopy (AFM). In vitro release mechanisms and permeation performance were evaluated before and after nanoparticles incorporation into the hydrogels. FTIR analysis was performed to evaluate the effect of formulation epidermal contact. Potential cytotoxicity was evaluated using the MTT reduction test and disc diffusion methods. The nanoparticle formulations were stable over 120 days with encapsulation efficiency (EE) of 60% and 99% for IR3535 and geraniol, respectively. AFM analysis revealed a spherical nanoparticle morphology. After 24 h, 7 ± 0.1% and 83 ± 2% of the GRL and IR3535, respectively, were released while the same formulation incorporated in poloxamer 407 hydrogel released 11 ± 0.9% and 29 ± 3% of the loaded GRL and IR3535, respectively. GRL permeation from PCL nanoparticles and PCL nanoparticles in the hydrogel showed similar profiles, while IR3535 permeation was modulated by formulation compositions. Differences in IR3535 permeated amounts were higher for PCL nanoparticles in the hydrogels (36.9 ± 1.1 mg/cm2) compared to the IR3535-PCL nanoparticles (29.2 ± 1.5 mg/cm2). However, both active permeation concentrations were low at 24 h, indicating that the formulations (PCL nanoparticles and PCL in hydrogel) controlled the bioactive percutaneous absorption. Minor changes in the stratum corneum (SC) caused by interaction with the formulations may not represent a consumer safety risk. The cytotoxicity results presented herein indicate the carrier systems based on poly-epsilon caprolactone (PCL) exhibited a reduced toxic effect when compared to emulsions, opening perspectives for these systems to be used as a tool to prolong protection times with lower active repellent concentrations.

Development of a Mosquito Repellent Formulation Based on Nanostructured Lipid Carriers.

Arboviral diseases are a threat to global public health systems, with recent data suggesting that around 40% of the world's population is at risk of contracting arboviruses. The use of mosquito repellents is an appropriate strategy to avoid humans coming into contact with vectors transmitting these viruses. However, the cost associated with daily applications of repellents can make their use unfeasible for the low-income populations that most need protection. Therefore, the development of effective formulations offers a way to expand access to this means of individual protection. Consequently, research efforts have focused on formulations with smaller quantities of active agents and sustained release technology, aiming to reduce re-applications, toxicity, and cost. The present study investigates the development of nanostructured lipid carriers (NLCs) loaded with a mixture of the compounds icaridin (synthetic) and geraniol (natural), incorporated in cellulose hydrogel. The NLCs were prepared by the emulsion/solvent evaporation method and were submitted to physicochemical characterization as a function of time (at 0, 15, 30, and 60 days). The prepared system presented an average particle size of 252 ± 5 nm, with encapsulation efficiency of 99% for both of the active compounds. The stability profile revealed that the change of particle size was not significant (p > 0.05), indicating high stability of the system. Rheological characterization of the gels containing NLCs showed that all formulations presented pseudoplastic and thixotropic behavior, providing satisfactory spreadability and long shelf life. Morphological analysis using atomic force microscopy (AFM) revealed the presence of spherical nanoparticles (252 ± 5 nm) in the cellulose gel matrix. Permeation assays showed low fluxes of the active agents through a Strat-M® membrane, with low permeability coefficients, indicating that the repellents would be retained on the surface to which they are applied, rather than permeating the tissue. These findings open perspectives for the use of hybrid formulations consisting of gels containing nanoparticles that incorporate repellents effective against arthropod-borne virus. These systems could potentially provide improvements considering the issues of effectiveness, toxicity, and safety.

Recent Developments in Nanotechnology for Detection and Control of Aedes aegypti-Borne Diseases.

Arboviruses such as yellow fever, dengue, chikungunya and zika are transmitted mainly by the mosquito vector Aedes aegypti. Especially in the tropics, inefficacy of mosquito control causes arboviruses outbreaks every year, affecting the general population with debilitating effects in infected individuals. Several strategies have been tried to control the proliferation of A. aegypti using physical, biological, and chemical control measures. Other methods are currently under research and development, amongst which the use of nanotechnology has attracted a lot of attention of the researchers in relation to the production of more effective repellents and larvicides with less toxicity, and development of rapid sensors for the detection of virus infections. In this review, the utilization of nano-based formulations on control and diagnosis of mosquito-borne diseases were discussed. We also emphasizes the need for future research for broad commercialization of nano-based formulations in world market aiming a positive impact on public health.