Chitosan-coated lipid nanocarriers co-delivering curcumin and α-terpinene with enhanced larvicidal activity against Cx. pipiens via oxidative stress.

The escalating global burden of mosquito-borne diseases, transmitted primarily by vectors such as Cx. pipiens, emphasizes the critical need for innovative and ecologically sustainable control agents. Addressing this challenge, this study focused on the synthesis and characterization of dual drug nanostructure lipid carrier loaded with natural compounds of curcumin and α-terpinene incorporated in lipid matrix (NLC-CA) and its chitosan-coated nanoformulation (NLC-CA@CS) for their effect as eco-friendly control of Cx. pipiens. The synthesized chitosan-coated nanosystems exhibited a core-shell structure with a particle size of 91.28 nm, a positive zeta potential (+ 22.9 mV), high encapsulation efficiency (> 72% for both actives), and significantly reduced cytotoxicity against normal WI-38 cells compared to free compounds. The larvicidal assay against Cx. pipiens larvae (24 h) revealed LC₅₀ values of 789.46 µg/mL (NLC-CA), 705.3 µg/mL (NLC-CA@CS), 821.08 µg/mL (α-terpinene), and 6967 µg/mL (curcumin). Mechanistically, this activity was attributed to the induction of pronounced oxidative stress, as evidenced by significant time- and concentration-dependent perturbations in antioxidant and lipid peroxidation biomarkers. Exposure to NLC-CA@CS triggered a significant increase in the superoxide anion radicals and lipid peroxidation, along with complex modulation of the antioxidant defense system, including superoxide dismutase (SOD) activity and total antioxidant capacity (TAC). These biochemical disruptions culminated in significant larval mortality at 1000 µg/mL after 24 h. The results collectively establish NLC-CA@CS, synthesized from natural compounds, as a good, target-selective, and biochemically active nano larvicide, positioning it as a promising candidate for sustainable vector management strategies.