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 (K_b = 1060) and βCD/IVER (K_b = 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 βCD. Finally, the inclusion of EPRI in βCD increased its larval toxicity and reduced its human cytotoxicity, while for IVER/βCD no beneficial effect was observed upon inclusion. These results were rationalized in terms of structural differences between the two molecules. Finally, the EPRI/βCD complex has great potential as an insecticide against A. aegypti larvae with high human safety.

中文翻译：

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β-环糊精/ Avermectins包合物的疏水性纳米沉淀物显示出对埃及伊蚊幼虫的杀虫活性和对成纤维细胞的低毒性

在本工作中，合成并表征了β-环糊精（βCD）与阿维菌素（EPRI）和伊维菌素（IVER）之间的阿维菌素（AVM）形成的包合物的疏水性纳米沉淀（HNP），并且它们对伊蚊和埃及伊蚊具有杀幼虫活性。评估了人类对成纤维细胞的安全性。最初，热重分析/差示热分析数据表明，存在βCD时，夹杂物增加了AVM的热稳定性。核磁共振实验和密度泛函理论计算指出，βCD腔中包含了两个AVM的苯并呋喃环。等温滴定量热法实验可以鉴定EPRI /βCD（K _b= 1060）和βCD/ IVER（K _b = 1700）系统，尽管结构相似。AVM的二甲基亚砜溶液在βCD水溶液中的动态光散射滴定表明，在存在βCD的情况下，形成的HNP尺寸较小。最后，在βCD中包含EPRI会增加其幼虫毒性并降低其人类细胞毒性，而对于IVER /βCD，在包含EPRI时未观察到有益作用。就两个分子之间的结构差异而言，这些结果是合理的。最后，EPRI /βCD复合物作为杀虫剂具有巨大的潜力，可对埃及伊蚊幼虫具有很高的人类安全性。