N,N-Diethyl-3-toluamide Formulation Based on Ethanol Containing 0.1% 2-Hydroxypropyl-β-cyclodextrin Attenuates the Drug’s Skin Penetration and Prolongs the Repellent Effect without Stickiness

Abstract

N,N-diethyl-3-toluamide (DEET) is one of the most widely used insect repellents in the world. It was reported that a solution containing 6–30% cyclodextrin (CD) as a solvent instead of ethanol (EtOH) provided an enhancement of the repellent action time duration of the DEET formulation, although the high-dose CD caused stickiness. In order to overcome this shortcoming, we attempted to prepare a 10% DEET formulation using EtOH containing low-dose CDs (β-CD, 2-hydroxypropyl-β-CD (HPβCD), methyl-β-CD, and sulfobutylether-β-CD) as solvents (DEET/EtOH/CD formulations). We determined the CD concentration to be 0.1% in the DEET/EtOH/CD formulations, since the stickiness of 0.1% CDs was not felt (approximately 8 × 10−3 N). The DEET residue on the skin superficial layers was prolonged, and the drug penetration into the skin tissue was decreased by the addition of 0.1% CD. In particular, the retention time and attenuated penetration of DEET on the rat skin treated with the DEET/EtOH/HPβCD formulation was significantly higher in comparison with that of the DEET/EtOH formulation without CD. Moreover, the repellent effect of DEET was more sustained by the addition of 0.1% HPβCD in the study using Aedes albopictus. In conclusion, we found that the DEET/EtOH/HPβCD formulations reduced the skin penetration of DEET and prolonged the repellent action without stickiness.

Poly(oxyethylene)/Poly(oxypropylene) butyl ether prolongs the repellent effect of N,N-diethyl-3-toluamide on the skin

“…The tensile stress of ICR mice was measured as described in our previous study [ 19 ]. Briefly, the dorsal and abdominal hair of the mice were removed.…”

“…The volatility of DEET formulations was measured according to a previous study [ 19 ]. DEET formulations were applied to absorbent cotton, and the weight of cotton with or without DEET formulations was measured.…”

“…Wistar rats were used to measure the POE-POP and DEET content in the skin tissue according to our previous study [ 19 ]. Briefly, the abdominal hair of rats were removed.…”

“…In addition, 15% Pluronic F127 micellar gel containing 10% DEET enhanced skin retention and drastically reduced skin permeation of the repellent [ 8 ]. We designed a DEET formulation using a combination of ethanol (EtOH) and 0.1% cyclodextrin as solvents, and observed reduced drug transdermal penetration and prolonged repellent effect compared with that of DEET formulation without cyclodextrin [ 19 ]. Thus, changes in the hydrophobicity and stabilization of DEET using polymers and cyclodextrin are expected to be promising strategies for DEET delivery.…”

A new fan-like adaptive porous organic cage for the structure determination of liquid perfume molecules

“…Compound 1 is a mosquito repellent. 21 It can also be used as a solvent for metal-organic framework synthesis. 22 The use of 1 increased because of the painful bite and spread of viruses by mosquitoes.…”