RESUMO
In the present work, hydrophobic nanoprecipitates (HNPs) of inclusion complexes formed between ß-cyclodextrin (ßCD) and the avermectins (AVMs) named eprinomectin (EPRI) and ivermectin (IVER) were synthesized and characterized, and their larvicidal activity against Aedes aegypti and human safety against fibroblasts were evaluated. Initially, thermogravimetric analysis/differential thermal analysis data revealed that inclusion increased the thermal stability of AVMs in the presence of ßCD. Nuclear magnetic resonance experiments and density functional theory calculations pointed out the inclusion of the benzofuran ring of the two AVMs in the ßCD cavity. Isothermal titration calorimetry experiments allowed identification of different binding constants for EPRI/ßCD ( Kb = 1060) and ßCD/IVER ( Kb = 1700) systems, despite the structural similarity. Dynamic light scattering titrations of AVMs' dimethyl sulfoxide solution in ßCD aqueous solution demonstrated that the formed HNPs have lower sizes in the presence of ßCD. Finally, the inclusion of EPRI in ßCD increased its larval toxicity and reduced its human cytotoxicity, while for IVER/ßCD no beneficial effect was observed upon inclusion. These results were rationalized in terms of structural differences between the two molecules. Finally, the EPRI/ßCD complex has great potential as an insecticide against A. aegypti larvae with high human safety.