Skin absorption as a key factor for determination of protection time in DEET-based mosquito repellent formulations against the Asian tiger mosquito, Aedes albopictus

Since the first discovery of its repellent activity against mosquitoes in 1946, N,N-diethyl-m-toluamide, DEET, has been the most frequently selected as an active ingredient of insect repellents around the globe. Although DEET has been applied onto human skin for more than 75 years in various formulations, understanding the impact of formulation types to the overall efficacy has been rarely explored. Moreover, vanillin has shown its boosting effect on the protection time of DEET, no clear explanation for the underlying synergy was proposed yet. In the present study, repellent activity was examined in 5 different formulations containing 5% of DEET, and carbopol, TiO2, and vanillin were added to those test products as potential boosting agents via novel in vivo indirect repellency assays which we designed to substitute hand-in-cage method. Among the formulations tested, ethanol, simple and complex O/W emulsions displayed the shortest protection time, and their protection times were significantly increased when vanillin was added. Notably, oil-based formulations including wax stick and W/S emulsion displayed much longer protection time even without the boosting agents, as showing similar protection times to those of vanillin-supplemented water-based formulations. Interestingly, neither vanillin nor TiO2 further increased protection time of oil-based ones, which indicates addition of vanillin to water-based formulation or applying oil-based formulation will guarantee longer protection time when using DEET as mosquito repellent. Skin permeation via a Franz cell assay was conducted to compare the difference in the absorption of DEET thorough mammalian skin to support the hypothesis.