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Sagun Poudel¹, Chaolong Qin¹, Rudra Pangeni¹

¹Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, USA.

|August 28, 2025

概括

研究人员开发了一种新的前期药物和A190的微乳液配方,一种PPARα激动剂,以改善治疗外围神经病的口服. 在大鼠中,A190- PD-60微乳液显著提高了生物可用性.

科学领域:

药理学
提供药物
代谢疾病

背景情况:

过氧体增殖器激活受体α (PPARα) 激动剂对于脂质代谢和治疗诸如外围神经病变等疾病至关重要.
现有的PPARα激动剂存在局限性,包括选择性差,生物可用性和安全性问题.
新型PPARα激动剂A190具有治疗潜力,但具有较差的溶解性和透性,阻碍了口服.

研究的目的:

合成和评估A190的新型前药物,以增强其口服.
制定和优化前药物候选物的微乳液,以改善药物动力学特性.
评估前药物微乳液策略在克服口服PPARα向疗法的生物可用性方面的有效性.

主要方法:

针对生物转化和稳定性的四种A190原药 (A190-PD-9,A190-PD-14,A190-PD-154,A190-PD-60) 的合成和评估.
使用Box-Behnken设计优化主要候选物A190-PD-60作为微乳液 (A190-PD-60-ME).
关于A190-PD-60-ME的特征包括液滴大小,多分散性,药物载荷和膜透性.
用于比较A190- PD-60- ME与A190- PD-60分散的口服生物利用性的大鼠药理学研究.

主要成果:

已确定循环碳酸盐前药物A190-PD-60为主要候选药物.
A190-PD-60-ME表现出纳米大小的滴 (~120 nm),低的PDI (<0.3),高的药物负载 (> 90%),以及增强的人工膜透性.
与A190- PD-60分散剂相比,A190- PD-60- ME的Cmax高出16. 6倍,相对口服生物可用性增加了5. 9倍.

结论:

开发的原药和微乳液配方有效地解决了A190的口服生物可用性限制.
综合前药物微乳液方法是推进PPARα向治疗的有希望的策略.
这种策略有可能用于治疗与脂质代谢失调相关的疾病,例如慢性外围神经病变.

关键词:

一种PPARα激动剂生物转化通过口服的生物利用性提供口服通过性

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