Larvicidal Activity of Naringenin: Betaine Cocrystals Against <i>Aedes Aegypti</i>

ABSTRACT Aedes aegypti is a vector of arboviruses, including dengue, Zika, chikungunya, and yellow fever. Increasing resistance to chemical insecticides has driven the search for sustainable larvicidal alternatives. This study evaluates the larvicidal activity of naringenin and betaine, individually, as a physical mixture, and after processing by liquid‐assisted grinding (LAG) and supercritical gas antisolvent (GAS) methods to determine whether solid‐state modification enhances activity. Cocrystal formation was confirmed for the GAS product by XRD, DSC, and FTIR, while the LAG sample showed solid‐state changes consistent with cocrystallization. SEM revealed reduced particle sizes, with the GAS product presenting the smallest mean diameter (27.60 ± 13.63 µm) compared with pure naringenin (88.76 ± 67.83 µm). In larvicidal assays, naringenin caused 91.33 ± 2.98% mortality at 90 mg L − 1 , whereas betaine showed no significant effect. Both processed samples improved efficacy: LAG and GAS products displayed lower LD 50 values (70.79 and 83.17 mg L − 1 ) than naringenin alone (106.17 mg L − 1 ) and the physical mixture (116.68 mg L − 1 ). The GAS product achieved 100% mortality at 90 mg L − 1 . These findings show that solid‐state modification and particle size reduction enhance the larvicidal potential of naringenin, highlighting supercritical technology as a promising and sustainable strategy for A. aegypti control.