使用可注射的In Situ交叉连接的仓库进行水友药物的超长期输送
Sohyung Lee1,2,3, Spencer Zhao2,3, Weihua Jiang4
1Harvard Medical School, Boston, MA, USA.
bioRxiv : the preprint server for biology
|September 10, 2024
概括
这项研究引入了一种新的可注射药物输送系统,用于在六个月内超长期释放水友药物. 新平台尽量减少初始药物爆发,并为慢性疾病提供更好的治疗潜力.
科学领域:
- 生物材料科学 生物材料科学
- 药物输送系统 药物输送系统
- 聚合物化学 聚合物化学
背景情况:
- 现有的长效注射剂 (LAI) 与水友性药物的超长期释放作斗争.
- 目前的平台,如现场成形植入物 (ISFI) 和微球,由于溶剂流出和大孔,分别遭受高爆发释放和快速扩散.
研究的目的:
- 开发一种新的可注射平台,用于水友性药物的超长期释放 (超过六个月).
- 克服当前LAI技术中出现的突发释放和快速扩散的局限性.
主要方法:
- 开发一个可注射平台,使用甲基化超低分子量聚烯酸前聚合物.
- 通过无溶剂工艺形成现场交叉连接仓库 (ISCD).
- 在老鼠体内研究以评估药物释放概况,并与ISFI进行比较.
主要成果:
- 在ISCD平台实现了超长期药物释放超过六个月的各种水友性药物 (抗逆转录病毒药物,抗生素,纳尔特雷) 和一种疏水性药物 (tacrolimus).
- 与ISFI相比,ISCD在老鼠模型中表现出明显较低的爆发释放和长时间的药物输送.
- 该系统能够同时提供水友药物组合,并允许通过设计参数调整释放动力学和降解.
结论:
- 开发的ISCD平台代表了实现水友药物超长期药物输送的突破.
- 药物动力学建模预测人类药物释放的时间超过六个月,超过目前的LAI能力.
- 该平台的生物降解性,可检索性和生物相容性为改善慢性疾病治疗坚持提供了重大潜力.
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