用于ARDS的等离子素-环氧德克斯特林喷雾剂:在模拟氧疗法和炎症触发的凝块溶解中保持活性
Lucia Vizzoni1, Chiara Migone2, Siria Emily Nesti2
1Department of Pharmacy, University of Pisa, Pisa, Italy; Department of Life Sciences, University of Siena, Siena, Italy.
International journal of pharmaceutics
|November 5, 2025
概括
一种新的可吸入配方可以保护等离子素 (PLG) 在雾化过程中不受氧化,从而保持其纤维解质活性,用于治疗急性呼吸困扰综合征 (ARDS). 这种方法增强了药物稳定性和肺部沉积,以有效地解决纤维素凝块.
科学领域:
- 肺部医学 肺部医学
- 生物技术是生物技术.
- 药理学 药理学是指药理学的学科.
背景情况:
- 急性呼吸困扰综合征 (ARDS) 的特征是严重的肺炎和纤维素沉积.
- 等离子素 (PLG) 是一种关键的纤维溶解剂,具有ARDS的治疗潜力,但在气溶化过程中容易受到氧化损伤.
- 目前对ARDS的治疗通常需要氧气治疗,并与有效的纤维素凝块去除作斗争.
研究的目的:
- 开发一种稳定,可吸入的等离子素 (PLG) 配方,使用基-β-环氧化 (HP-β-CD) 来保护它免受雾化过程中的氧化降解.
- 为了评估配方的空气动力学特性,肺部沉积和在富含氧气的条件下保存的酶活性.
- 在凝块溶解模型中证实雾化PLG配方在体外纤维溶解疗效.
主要方法:
- 使用光谱分析 (FT-IR) 确认了PLG与HP-β-CD的并发症.
- 氧化稳定性通过基于计算机的调查和FT-IR进行评估,重点是 metionin 残留物.
- 使用网状雾化 (MMAD,FPF) 评估了空气动力学性能.
- 雾化后的酶活性被测量为氧气流量.
- 在体外血栓溶解被评估使用尿素酶触发和细胞激活的模型,与D-二分体量化.
主要成果:
- 惠普-β-CD复合保护了PLG的氨酸残留物免受氧化,通过光谱学和计算分析证实了这一点.
- 可吸入的配方显示出有利的肺沉积特征 (MMAD ~2.1 μm,FPF ~84%).
- 与HP-β-CD复合的雾化PLG在氧气流中保留了95%以上的酶活性,明显高于未受保护的PLG (~57%).
- 这种配方在尿素酶触发和巨细胞激活模型中有效溶解人体凝块,通过D-二聚合物水平进行验证.
结论:
- 在临床上可行的,可吸入的PLG配方复合HP-β-CD有效地保持在氧气下雾化期间的酶活性.
- 该配方表现出适合肺部输送的空气动力学特性,并表现出强大的体外纤维溶解能力.
- 这种方法为ARDS的向性纤维溶解疗法提供了一个有希望的策略,促进了临床转化.
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