双模块 - - 具有分子印记贴片功能的双模块,用于通过皮肤输送的种族药物的酶选择性控制释放,用于通过皮肤输送
Yang Zhang1, Xiaowen Liu2, Jiaxu Wu1
1Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, Liaoning 110016, China.
International journal of pharmaceutics
|September 16, 2024
概括
这项研究引入了一种用于透皮药物输送的新性分子印记贴片 (CMIP). 在CMIP选择性释放治疗性S-enantiomers,同时抑制R-enantiomers,增强疗效和减少副作用.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 奇拉化学 奇拉化学
背景情况:
- 通过皮肤递送药物系统 (TDDS) 经常使用种族药物,其中90%以上是反体的混合物.
- 种族混合物中异构体 (不需要的异构体) 的存在可能会增加不良副作用的风险,并降低治疗效率.
- 为改善治疗结果和患者安全,开发对抗选择性药物递送的方法至关重要.
研究的目的:
- 设计和开发一种能够在TDDS中选择性控制药物反体释放的奇拉分子印记贴片 (CMIP).
- 为了获得优选释放的eutomer (S-enantiomer) 和同时抑制的分离体 (R-enantiomer) 改善治疗结果.
- 调查CMIP内的反选择性释放和吸附过程背后的分子机制.
主要方法:
- 通过结合形压敏粘合剂 (PSA) 和分子印制聚合物 (MIP) 来制造CMIP.
- 在体外和体内研究,以评估S-enantiomers与R-enantiomers的通过皮肤传递效率.
- 利用合成的光探头体来可视化和确认选择性释放过程.
- 分子机制研究,包括分析性相互作用 (H键,π-π,范德瓦尔斯力) 和空间形态依赖.
主要成果:
- 与R-enantiomers相比,CMIP显示S-enantiomers的通过皮肤递送显著增强,体外增加1.86倍,体内增加3.74倍.
- CMIP有效地抑制了R-enantiomers的释放,从而降低了二元体的总体摄入量.
- 光探针反体成功可视化了反选择性释放机制.
- 分子调查显示,MIP和PSA内的空间构造和性相互作用是对enantioselective控制的关键.
结论:
- 开发的CMIP提供了一种创新的方法,用于酶选择性透皮药物递送,使优选释放eutomers和抑制distomers.
- 这项技术具有显著的潜力,可以提高治疗效率,并最大限度地降低与TDDS中奇拉药物相关的过量剂量风险.
- 这些发现突显了分子设计和性相互作用在实现向药物递送和增强药理成果方面的重要性.
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