用于向中枢神经系统输送广谱神经毒剂解毒剂的循环德克斯基配方:稳定性,物理化学表征和在人类血脑屏障模型中的应用
Léa Thiberville1, Vincent Faivre2, Christina Sizun3
1Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, 91400 Orsay, France; Ecole de Chimie Polymères et Matériaux, Université de Strasbourg, Institut de Chimie et Procédés pour l'Energie, l'Environnement et la Santé UMR CNRS 7515, 67087 Strasbourg, France.
International journal of pharmaceutics
|March 25, 2025
概括
循环德克斯的配方增强了神经毒剂抗毒剂JDS364.HCl的稳定性,提高了其作为治疗对策的潜力. 这些配方通过增加稳定性和血兼容性,显示出更好的神经毒剂治疗的前景.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物输送系统 药物输送系统
- 毒理学 毒理学 毒理学
背景情况:
- 像VX和沙林这样的神经毒剂对安全构成重大威胁.
- 目前的解毒剂的治疗效果有限,需要新的解决方案.
- JDS364.HCl是一种有前途的神经毒剂抗毒剂,但其水性稳定性不佳.
研究的目的:
- 为了提高JDS364.HCl的稳定性,使用基于循环德克斯的配方.
- 评估循环德克斯复合对JDS364.HCl稳定性和血脑屏障 (BBB) 透性的影响.
- 为了比较HP-β-CD和SBE-β-CD配方在JDS364.HCl输送中的疗效.
主要方法:
- 使用HP-β-CD和SBE-β-CD的JDS364.HCl的配方. 这种配方是
- 在室温下水溶液和血中的稳定性研究.
- 使用相互作用研究来测结体和亲和度常数的确定.
- 使用人类BBB模型评估BBB透性.
主要成果:
- 两种HP-β-CD和SBE-β-CD配方都显著改善了JDS364.HCl的稳定性,持续了两个多月.
- JDS364.HCl:SBE-β-CD复合体的亲和力常数比JDS364.HCl:HP-β-CD.高100倍.
- SBE-β-CD提供了卓越的血稳定性,但高亲和力影响了BBB透.
- 这两种配方都提高了血稳定性,并允许BBB通过,而JDS364.HCl显示出比2-PAM更好的BBB透性.
结论:
- 循环德克斯林复合有效地稳定了JDS364.HCl,解决了其固有的不稳定性.
- HP-β-CD和SBE-β-CD配方显示出提高神经毒剂抗剂功效的潜力.
- 可能需要进一步优化,以平衡稳定性和释放动力学,以获得最佳的治疗结果.
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