Hydrophobic Nanoprecipitates of β-Cyclodextrin/Avermectins Inclusion Compounds Reveal Insecticide Activity against Aedes aegypti Larvae and Low Toxicity against Fibroblasts

In the present work, hydrophobic nanoprecipitates (HNPs) of inclusion complexes formed between β-cyclodextrin (βCD) 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 βCD. Nuclear magnetic resonance experiments and density functional theory calculations pointed out the inclusion of the benzofuran ring of the two AVMs in the βCD cavity. Isothermal titration calorimetry experiments allowed identification of different binding constants for EPRI/βCD (Kb = 1060) and βCD/IVER (Kb = 1700) systems, despite the structural similarity. Dynamic light scattering titrations of AVMs’ dimethyl sulfoxide solution in βCD aqueous solution demonstrated that the formed HNPs have lower sizes in the presence of β...