Bhattaccharjee Sonalika Arup, Junaid Mohammad Shajid Ashraf, Ghosh Meheli, Srivastava Ritesh, Athar Mohammad, Banga Ajay K
Center for Drug Delivery and Research, Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, Georgia, 30341, USA.
Department of Dermatology, UAB Research Center of Excellence in Arsenicals, University of Alabama at Birmingham, Birmingham, Alabama, USA.
AAPS PharmSciTech. 2025 Jul 1;26(6):178. doi: 10.1208/s12249-025-03177-6.
Being highly toxic and a quick-acting vesicant, even small amounts of lewisite if not decontaminated immediately are rapidly absorbed into systemic circulation via skin exposure, leading to acute poisoning and death. The skin is the first major target to such chemical weapons. Although the stratum corneum provides a barrier lewisite being a lipophilic molecule that readily permeates this barrier. This necessitates, making early and thorough decontamination prior to manifestation of adverse effects. For this, we aimed to decontaminate skin using an antidote-loaded topical foam, followed by treating local and systemic toxicity using the same formulation. Successful incorporation of 1% antidote into a decontaminating topical foam and the delivery of 1.78 ± 0.21 µg/sq cm into dermatomed porcine ear skin within five minutes of application was achieved. Decontamination after five minutes of exposure (88.43%), as well as prolonged exposure (94.53%; 3 h) to methyl salicylate, a warfare chemical simulant, was demonstrated. The developed formulation demonstrated the potential to back-extract simulant from skin tissue but could not purge simulant penetrated systemic circulation. However, systemic delivery of the antidote was demonstrated, establishing the potential to treat the toxicity caused by the remnant warfare chemicals.
路易氏剂具有高毒性且是一种速效糜烂性毒剂，即使是少量的路易氏剂，如果不立即进行去污处理，通过皮肤接触也会迅速被吸收进入体循环，导致急性中毒甚至死亡。皮肤是这类化学武器的首要主要目标。尽管角质层提供了一道屏障，但路易氏剂是一种亲脂性分子，很容易穿透这道屏障。因此，必须在不良反应出现之前尽早进行彻底去污处理。为此，我们旨在使用负载解毒剂的局部泡沫对皮肤进行去污，然后使用相同配方治疗局部和全身毒性。成功将1%的解毒剂掺入去污局部泡沫中，并在应用后五分钟内将1.78±0.21微克/平方厘米的解毒剂输送到去角质的猪耳皮肤中。结果表明，在接触模拟战剂水杨酸甲酯五分钟后（去污率88.43%）以及长时间接触（94.53%；3小时）后均有去污效果。所开发的配方显示出从皮肤组织中反萃取模拟剂的潜力，但无法清除已渗透进入体循环的模拟剂。然而，已证明解毒剂可进行全身给药，这表明有潜力治疗残留战剂造成的毒性。
