Triple-Olfactory Mechanism Synergy: Development of a Long-Lasting DEET–Botanical Composite Repellent Against Aedes albopictus

Mosquito-borne diseases, including dengue fever, chikungunya, and Zika, continue to pose a substantial global public health challenge. This is largely attributable to the absence of effective vaccines and the expanding distribution of vectors such as Aedes albopictus (Ae. albopictus). Repellents, therefore, remain a critical component of prevention strategies for disease prevention. However, existing formulations have notable limitations. Synthetic repellents such as DEET provide broad-spectrum efficacy but may raise safety concerns, especially at high concentrations. In contrast, botanical repellents, such as citronella and camphor oils, offer more favorable safety profiles but are restricted by short protection durations due to their high volatility. To overcome these drawbacks, this research developed a composite mosquito repellent through the strategic combination of DEET (5–15%), citronella oil (10–20%), and camphor oil (5–15%). This formulation leverages interactions across multiple olfactory pathways to simultaneously enhance efficacy and reduce the DEET concentration. Orthogonal experimental optimization identified an optimized formulation, Mix-3 (consisting of 15% DEET, 15% citronella oil, and 10% camphor oil in 75% ethanol), which achieved a mean complete protection time of 9.45 h. Mix-3 provided longer protection than 7% DEET (mean difference = 5.50 h, p < 0.001), 4.5% IR3535 (2.83 h, p < 0.001), 10% citronella oil (3.58 h, p < 0.001), and 15% DEET (6.50 h, p < 0.001). Catnip oil did not contribute significantly to repellency (p = 0.895). This study demonstrates that the rational combination of synthetic and botanical repellents effectively overcomes the limitations of single-agent formulations, providing a long-lasting and scalable approach for vector control.