Microneedle-mediated transdermal delivery of N-acetyl cysteine as a potential antidote for lewisite injury.
Microneedle-mediated transdermal delivery of N-acetyl cysteine as a potential antidote for lewisite injury.
复制标题
微针介导的 N-乙酰半胱氨酸透皮递送作为路易斯损伤的潜在解毒剂。
DOI：
10.1016/j.ijpharm.2023.123547
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发表时间：
2023
影响因子：
5.8
通讯作者：
Banga,AjayK
中科院分区：
文献类型：
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作者：
Kshirsagar,Sharvari;Dandekar,Amruta;Srivastava,RiteshK;Khan,Jasim;Muzaffar,Suhail;Athar,Mohammad;Banga,AjayK
路易氏剂是一种用于世界大战的化学战剂，由于库存或意外接触而对平民构成潜在威胁。路易氏剂介导的皮肤损伤的特征是急性红斑、疼痛和水疱形成。 N-乙酰半胱氨酸 (NAC) 是 FDA 批准的一种治疗对乙酰氨基酚毒性的药物，被认为是路易斯特的潜在解毒剂。在本研究中，我们探索了通过透皮途径快速递送NAC以潜在治疗化学战毒性的可行性。 NAC 是一种小的亲水分子，通过皮肤的被动传递有限。在我们的研究中，使用带有溶解微针的皮肤微孔显着增强了 NAC 进入和穿过皮层人体皮肤的输送。与穿刺和凝胶方法 (474.91 ± 70.09 µg/sq·cm) 和载药微针相比，微孔化后应用溶液 (穿刺和溶液) 产生最高的体外递送 (509.84 ± 155.04 µg/sq·cm) （226.89 ± 33.41 微克/平方厘米）。通过穿刺和溶液方法递送 NAC 的滞后时间 (0.23 ± 0.04 h) 接近于凝胶应用 (0.25 ± 0.02 h)，载药微针的滞后时间最高 (1.27 ± 1.16 h)。因此，我们成功证明了使用各种皮肤微孔化方法快速递送 NAC 的可行性，以潜在治疗路易斯介导的皮肤毒性。
Lewisite is a chemical warfare agent intended for use in World War and a potential threat to the civilian population due to presence in stockpiles or accidental exposure. Lewisite-mediated skin injury is characterized by acute erythema, pain, and blister formation. N-acetyl cysteine (NAC) is an FDA-approved drug for acetaminophen toxicity, identified as a potential antidote against lewisite. In the present study, we have explored the feasibility of rapid NAC delivery through transdermal route for potentially treating chemical warfare toxicity. NAC is a small, hydrophilic molecule with limited passive delivery through the skin. Using skin microporation with dissolving microneedles significantly enhanced the delivery of NAC into and across dermatomed human skin in our studies. Microporation followed by application of solution (poke-and-solution) resulted in the highestin vitrodelivery (509.84 ± 155.04 µg/sq·cm) as compared to poke-and-gel approach (474.91 ± 70.09 µg/sq·cm) and drug-loaded microneedles (226.89 ± 33.41 µg/sq·cm). The lag time for NAC delivery through poke-and-solution approach (0.23 ± 0.04 h) was close to gel application (0.25 ± 0.02 h), with the highest for drug-loaded microneedles (1.27 ± 1.16 h). Thus, we successfully demonstrated the feasibility of rapid NAC delivery using various skin microporation approaches for potential treatment against lewisite-mediated skin toxicity.