DEET-cyclodextrin inclusion complexes for mosquito and tick repellency: extended repellency time and no zebrafish embryotoxicity

Abstract

Background: Repellent formulations are a cost-effective strategy for protection against disease vectors. N,N-diethyl-meta-toluamide (DEET) is widely used to repel mosquitoes and ticks, including Amblyomma sculptum, the vector of Rickettsia rickettsii (the agent of Brazilian spotted fever), and Aedes aegypti, responsible for dengue, zika, and chikungunya. This study aimed to develop cyclodextrin (CD)-DEET complexes for topical application. Phase-solubility studies identified the most suitable CD, and hydroxypropyl-β-cyclodextrin (HPβCD)-DEET was selected for further investigation. In vitro release and skin permeation were evaluated. Embryotoxicity was assessed in a zebrafish model, and repellent efficacy was investigated against both species. Results: Phase-solubility studies revealed AL-type profiles for αCD, γCD, and HPβCD, with slopes between 1 and 2, and K2:1 values of 4738, 4494, and 2169, respectively. HPβCD-DEET exhibited slower DEET release compared to the control (26.7% vs 50.4% over 10 h, P < 0.05). Although DEET permeation to the receptor medium was similar (P > 0.05), HPβCD reduced DEET retention in the stratum corneum by 2.6-fold (P < 0.05). HPβCD-DEET did not cause embryotoxicity in permeated DEET concentrations (69 mg L-1). Repellency bioassays showed HPβCD-DEET efficacy against A. sculptum for 168 h (80.5-100%) and full protection against A. aegypti for 7 h (>95%). Conclusion: These results highlight the potential of HPβCD-DEET complexes for safer and effective repellent formulations.