(350y) Enabling Nano-Insecticides: Biodegradable Nanoparticle Biodistribution in Aedes Aegypti Mosquitoes

Mosquito-borne illnesses cause millions of cases and hundreds of thousands of deaths every year, and insecticide resistance poses a threat to attempts to control their populations. Successful insecticides must migrate through the cuticle, distribute among physiologically relevant tissues, and reach sufficient accumulation at the target site to achieve a toxic effect. Complex and distinct physicochemical requirements imposed by each biological barrier contribute a significant, cumulative hurdle for successful delivery of new insecticides. Micro- and nanoparticle drug delivery carriers are designed to navigate such biological barriers to improve therapeutic and prophylactic payload delivery to target sites. Their pharmacological potentiation capabilities have been relatively underexplored for insecticides, but could expand the palette of insect control strategies and improve the activity of existing compounds.

Microparticles and nanoparticles were synthesized from two formulations of rhodamine B end group-functionalized polyanhydride copolymers and used to treat Aedes aegypti mosquitoes by three field-relevant exposure routes: surface, topical, and per os. Microparticles were observed to associate with mosquitoes to a much lesser extent than nanoparticles, regardless of chemistry, after treated surface exposure. Nanoparticle chemistry-associated differences were observed for both external labeling and labeling of the pharmacologically relevant malpighian tubules, midgut, and ovarian internal tissues. Both nanoformulations significantly labeled at least one internal tissue in all three exposure routes, while soluble rhodamine B was unable to label these tissues after topical exposure. This provides powerful evidence that these nanocarriers can guide payloads past the cuticle into target tissues that are unable to accomplish such transport on their own. Across all exposure routes, the more amphiphilic nanoparticle chemistry achieved more intense labeling of internal tissues than the more hydrophobic chemistry. Neither particle chemistry under any exposure route caused increased mortality for the first five days of any treatment.

Collectively, these observations indicate polyanhydride nanoparticles capabilities to navigate arthropod vector biological barriers, motivating further exploration of nanocarriers for active insecticidal compound delivery. Particle chemistry and exposure route can be tailored to target insecticidal molecules to specific, pharmacologically relevant tissues within insects, or enable the broad internal distribution of such compounds within Ae. aegypti mosquitoes. Such capabilities could contribute to the next generation of insecticidal interventions by improving potency and potentiating novel insecticidal mechanisms.