Fabrication of an Effective Avermectin Nanoemulsion Using a Cleavable Succinic Ester Emulsifier

In this study, a new emulsifier precursor was prepared via esterification of avermectin with succinic anhydride. The chemical structure of the product was confirmed to be monosubstituted avermectin. After neutralization with triethanolamine, it exhibited adequate emulsification ability for avermectin. Avermectin was then encapsulated in nanoparticles in the nanoemulsion with a high drug loading up to 60 wt % and high stability. The nanoemulsion of nanoparticles that serves as a carrier of avermectin shows highly efficient pesticide characteristics, including low surface tension, high affinity to leaves, and improved photostability. In the presence of esterase or under strongly basic conditions, the ester bonds of the emulsifier can be hydrolyzed, and the encapsulated avermectin molecules can be released in an accelerated manner. The nanoemulsion exhibited improved insecticidal effect compared with commercial emulsifiable concentrate, which was attributed to the cleavage of ester bonds of the emulsifier by esterase in vivo

Fabrication of Novel Avermectin Nanoemulsion Using a Polyurethane Emulsifier with Cleavable Disulfide Bonds

In this study, a polyurethane emulsifer with various functional groups was prepared from isophorone diisocyanate, avermectin, 2,2-dimethylol propionic acid, and bis­(2-hydroxyethyl) disulfide. The chemical structure of the polymer was confirmed by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, and element analysis. The polymer exhibited adequate emulsification ability for avermectin after neutralization with triethylamine. A satisfaying nanoemulsion was obtained, in which avermectin was encapsulated in nanoparticles with 50 wt % drug loading, low organic solvent content, and high stability under dilution and centrifuging treatment in addition to low surface tension, high affinity to crop leaf, and improved avermectin photostability. The resulting nanoparticles showed degradability in the presence of dl-dithiothreitol or inside the insect as a result of the disulfide bonds, promoting the release of avermectin. As a result, the avermectin nanoparticles showed higher insecticidal ability compared to both the avermectin nanoparticles without a disulfide group and the avermectin emulsifiable concentrate

Metabolism and Bioactivation of Fluorochloridone, a Novel Selective Herbicide, in Vivo and in Vitro

Fluorochloridone (FLC) is a herbicide used worldwide that is thought to be safe. However, due to its potential genotoxicity, cytotoxicity, and even systematic toxicity, there are increasing concerns about human exposure to this compound. Thus, the metabolism and bioactivation of FLC was investigated. After oral administration to mice, 27 metabolites were identified by ultrahigh performance liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry and with further structural identification by nuclear magnetic resonance spectroscopy. Hydroxylation and oxidative dechlorination were the major phase I pathways, while glutathione (GSH) and <i>N</i>-acetylcysteine conjugations were two major phase II pathways, indicating the formation of a reactive intermediate. In vitro microsomal and cytosolic studies revealed that a GSH conjugate (M13) was the predominant metabolite of FLC formed through a nucleophilic S_N2 substitution of 3-Cl by GSH; this pathway is NADPH independent and accelerated by glutathione <i>S</i>-transferase (GST). Further, a kinetic study showed that M13 formation in both human liver microsomes and cytosols obeyed typical Michaelis–Menten kinetics. The maximum clearance (<i>V</i>_max/<i>K</i>_m) of GSH conjugation in human liver microsomes was approximately 5.5-fold higher than human liver cytosol, thus implying that microsomal GST was mainly responsible for M13 formation. These findings are important for understanding the potential hazard of human exposure to FLC