Binding affinity and decontamination of dermal decontamination gel to model chemical warfare agent simulants

Abstract

Six chemical warfare agent simulants (trimethyl phosphate, dimethyl adipate, 2-chloroethyl methyl sulfide, diethyl adipate, chloroethyl phenyl sulfide and diethyl sebacate) were studied in in vitro human skin to explore relationship between dermal penetration/absorption and the mechanisms of simulant partitioning between stratum corneum (SC) and water as well as between dermal decontamination gel (DDGel) and water. Both binding affinity to and decontamination of simulants using DDGel were studied. Partition coefficients of six simulants between SC and water (Log P ) and between DDGel and water (Log P ) were determined. Results showed that DDGel has a similar or higher binding affinity to each simulant compared to SC. The relationship between Log P octanol/water and Log P as well as between Log P octanol/water and Log P demonstrated that partition coefficient of simulants correlated to their lipophilicity or hydrophilicity. Decontamination efficiency results with DDGel for these simulants were consistent with binding affinity results. Amounts of percentage dose of chemicals in DDGel of trimethyl phosphate, dimethyl adipate, 2-chloroethyl methyl sulfide, diethyl adipate, chloroethyl phenyl sulfide and diethyl sebacate were determined to be 61.15, 85.67, 75.91, 53.53, 89.89 and 76.58, with corresponding amounts absorbed in skin of 0.96, 0.65, 1.68, 0.72, 0.57 and 1.38, respectively. In vitro skin decontamination experiments coupled with a dermal absorption study demonstrated that DDGel can efficiently remove chemicals from skin surface, back-extract from the SC, and significantly reduced chemical penetration into skin or systemic absorption for all six simulants tested. Therefore, DDGel offers a great potential as a NextGen skin Decon platform technology for both military and civilian use.

Effect of iron and silica nanoparticles’ size on in vitro human skin binding and penetration

“…34 Chemicals’ binding affinities to SC protein/lipids are associated with their skin permeability. 35 As presented in Table 2 after 24 h of incubation, SC binding rate of 32 nm Fe 3 O 4 @SiO 2 was also four times of that of 33 nm SiO 2 . The results suggest that Fe 3 O 4 NPs have higher SC affinity than that of SiO 2 NPs.…”

Follicular pathway role in chemical warfare simulants percutaneous penetration

“…Frumet et al (2007) showed that maximal follicular contribution occurs with chemicals with intermediate Log P o/w values. Cao et al (2018) suggested that there is a little correlation between partitioning into SC and Log P o/w indication that SC is a less significant barrier for less lipophilic penetrants. Another study (Wu, Ramachandran, Weiner, & Roessler, 2001) suggested that actually sebaceous gland secretion could favor penetration of emulsions with higher lipophilicity.…”