Polymeric Nanorepellent Systems Containing Geraniol and Icaridin Aimed at Repelling Aedes aegypti

Abstract

Repellents are among the leading products used against diseases transmitted by the Aedes aegypti mosquito. However, their indiscriminate use or high concentrations can cause severe adverse reactions, particularly in children and pregnant women. To protect them, nanotechnology is a promising tool to encapsulate active compounds against degradation, increase their effectiveness, and decrease their toxicity, as it can promote the modified release of the active compound. This study aimed to develop polymeric nanocapsules containing the repellent actives geraniol and icaridin using low concentrations of the active component, with the objective of promoting effective activity and greater safety against adverse reactions. The nanocapsules were developed by the interfacial deposition method, and the physicochemical properties of the nanocapsules were evaluated using dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), zeta potential, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), release kinetics assay, and mathematical modeling. Cell viability was assessed by the MTT assay and genotoxicity analysis using the comet assay. The developed nanocapsules containing geraniol and icaridin showed mean diameters of 260 nm and 314 nm, respectively, with a polydispersity index < 0.2. The nanocapsules showed encapsulation efficiency values of 73.7 ± 0.1% for icaridin and 98.7 ± 0.1% for geraniol. Morphological analysis showed spherical nanocapsules with low polydispersity. The kinetic parameters calculated using the Korsmeyer−Peppas model indicated an anomalous release profile. Cell viability and genotoxicity analyses showed that the nanocapsules did not alter cell viability or damage DNA. The results demonstrate a promising nanostructured system with good physicochemical characteristics and good stability, with repellent activity against Aedes aegypti.

Keywords: Aedes aegypti; geraniol; icaridin; nanocapsules.

Figure 1

(A) Macroscopic view of the Nano_Control polymeric nanocapsule formulations: (a) Nano_Control; (b) Nano_GER1%—Nanocapsules containing 1% of geraniol; (c) Nano_GER3%—Nanocapsules containing 3% of geraniol; (d) Nano_ICAR1%—Nanocapsules containing 1% icaridin and (e) Nano_ICAR3%—Nanocapsules containing 3% icaridin. (B) pH profile of PCL polymeric nanocapsules containing geraniol and icaridin (0, 15, 30, 60 days, and 90 days). Measurements were performed in triplicate (n = 3).

Figure 2

Hydrodynamic diameter (size) of polymeric nanocapsules containing geraniol and icaridin as a function of time (90 days). Measurements were performed in triplicate (n = 3); these values represent the mean of the three determinations. Considered significance of p < 0.05 (one-way ANOVA—Tukey) for the analysis of variance of times (15, 21, 30, 60, and 90 days) in relation to time 0. Equal symbols (α, σ, δ, Φ and γ) represent significant variation.

Figure 3

Results of polydispersity index (PDI) determinations of polymeric nanocapsules containing geraniol and icaridin as a function of time from 0 to 90 days. Measurements were performed in triplicate (n = 3).

Figure 4

Particle size distribution as a function of concentration and time (0, 8, 15, 21, 30, 60, and 90 days) of the formulations (a) Nano_Control, (b) Nano_GER1%, (c) Nano_GER3%, (d) Nano_ICAR1%, and (e) Nano_ICAR3% using Nanoparticle Tracking Analysis (NTA).

Figure 5

Differential exploratory calorimetry thermograms for: Nano_Control, Nano_GER1%, Nano_GER3%, Nano_ICAR1%, Nano_ICAR3%, and PCL.

Figure 6

(a) Infrared spectra for the bioactives geraniol and icaridin and (b) infrared spectra for the formulations Nano_Control, Nano _GER1%, Nano_GER3%; Nano_ICAR1%, and Nano _ICAR3%. The spectra were obtained through Fourier transform infrared spectroscopy (FTIR) using KBr, in the frequency range from 4000 to 400 cm⁻¹.

Figure 7

Encapsulation efficiency (%) of polymeric nanocapsules as a function of time (0, 15, 21, 30, 60, and 90 days). Measurements were performed in triplicate (n = 3); these values represent the mean of the three determinations. Considered significance of p < 0.05 (one-way ANOVA—Tukey) for the analysis of variance of times (15, 21, 30, 60, and 90 days) in relation to time 0. Equal symbols (α, σ, δ and Φ) represent significant variation.

Figure 8

Representation of the size distribution graph (nm) in relation to relative frequency (%) and topography referring to the Nano_GER3% formulation.

Figure 9

Representation of the size distribution graph (nm) in relation to relative frequency (%) and topography referring to the Nano_ICAR3% formulation.

Figure 10

Chemical structures of Poly-ε-caprolactone (PCL), geraniol and icaridin.

Figure 11

The graph shows cumulative release curves (%) of Nano_GER3% nanocapsules: Nano_ICAR3%, Emulsion_GER3%, and Emulsion_ICAR3% were carried out at a temperature of 32 °C. The analyses were performed in triplicate (n = 3) and quantification by high-performance liquid chromatography (HPLC).

Figure 12

Cytotoxicity evaluation of formulations (a) Nano_GER3%/ICAR3% and (b) Nano_Control on 3T3 and V79 cell lines.

Figure 13

DNA damage assessment by the comet assay in cell lines: 3T3 and V79 exposed to concentrations of 0.005; 0.01, and 0.02 mg/mL of the formulations Nano_GER/ICAR3% and Nano_S/Active. Equal numbers (a1, b1) are not statistically significant (p > 0.05).