Biodistribution of degradable polyanhydride particles in Aedes aegypti tissues.

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 mu m), labeled with rhodamine B to associate with and/or transit across insect biological barriers, including the cuticle, epithelium, midgut and ovaries, in femaleAe.aeygptimosquitoes. Mosquitoes were exposed using conditions to mimic surface contact with a residual spray or paint, topical exposure to mimic contact with aerosolized insecticide, orper osin 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, orper 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 withAedes aegyptiAag2 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. Author summary To expand the repertoire of insecticides available for public health purposes, we explored the potential of biodegradable polyanhydride nanoparticles for localizing within specific tissues within the yellow fever mosquito,Aedes aegypti, after a variety of exposures. These nanoparticles successfully migrated across the insect cuticle, one of the primary barriers to insecticide potency, and localized within specific tissues observed in this study. We also demonstrated that these nanoparticles associated with an insect cell line and were internalized within these cells. In all exposures, these nanoparticles did not produce toxicity to the exposed organisms, making them ideal carriers for future insecticides. This study demonstrates the utility of these biodegradable nanoparticles in the future of insecticide development.