Abstract
Insecticide resistance poses a significant threat to the control of arthropods that transmit disease agents. Nanoparticle carriers offer exciting opportunities to expand the armamentarium of insecticides available for public health and other pests. Most chemical insecticides are delivered by contact or feeding, and from there must penetrate various biological membranes to reach target organs and kill the pest organism. Nanoparticles have been shown to improve bioactive compound navigation of such barriers in vertebrates, but have not been well-explored in arthropods. In this study, we explored the potential of polyanhydride micro- and nanoparticles (250 nm– 3 μm), labeled with rhodamine B to associate with and/or transit across insect biological barriers, including the cuticle, epithelium, midgut and ovaries, in female Ae. aeygpti mosquitoes. Mosquitoes were exposed using conditions to mimic surface contact with a residual spray or paint, topical exposure to mimic contact with aerosolized insecticide, or per os in a sugar meal. In surface contact experiments, microparticles were sometimes observed in association with the exterior of the insect cuticle. Nanoparticles were more uniformly distributed across exterior tissues and present at higher concentrations. Furthermore, by surface contact, topical exposure, or per os, particles were detected in internal organs. In every experiment, amphiphilic polyanhydride nanoparticles associated with internal tissues to a higher degree than hydrophobic nanoparticles. In vitro, nanoparticles associated with Aedes aegypti Aag2 cells within two hours of exposure, and particles were evident in the cytoplasm. Further studies demonstrated that particle uptake is dependent on caveolae-mediated endocytosis. The propensity of these nanoparticles to cross biological barriers including the cuticle, to localize in target tissue sites of interest, and to reach the cytoplasm of cells, provides great promise for targeted delivery of insecticidal candidates that cannot otherwise reach these cellular and subcellular locations.
Highlights
The uptake and biodistribution of an insecticidal active ingredient in target arthropod species is fundamental to its efficacy and to formulation of end use products
Functionalized 20:80 CPH:sebacic acid (SA) and 20:80 CPTEG:CPH copolymers were synthesized by a one pot, two step reaction scheme wherein the carboxylic acid group of rhodamine B (Rho) was replaced by an anhydride group, followed by covalent conjugation of Rho to the polymer with an anhydride bond via melt condensation (Fig 1A)
The 20:80 CPTEG:CPH particles were more often observed in association with internal tissues than the 20:80 CPH:SA particles, and had consistently higher mean fluorescence intensity (MFI) values (Fig 5B)
Summary
The uptake and biodistribution of an insecticidal active ingredient in target arthropod species is fundamental to its efficacy and to formulation of end use products. The complex and distinct physicochemical requirements for clearing each of the biological barriers that an insecticide encounters present a significant, cumulative hurdle for successful delivery of new insecticides. Compounding this problem, vertebrate animal toxicity and environmental contamination concerns may limit the applicability of an otherwise promising candidate active ingredient. Certain classes of insecticides can cause environmental contamination of soil and water resources, non-target toxicity, and have been linked to a wide array of human maladies [5,6]
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