异物反应对从皮下输送系统的药物化的影响
Simone Capuani1, Nathanael Hernandez1, Jocelyn Nikita Campa-Carranza2
1Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
Biomaterials
|January 17, 2025
概括
对药物输送植入物的异体反应 (FBR) 对小分子药物释放的长期影响很小. 虽然急性FBR可能会暂时影响大量的蛋白质释放,但纤维化封装不会显著改变稳定状态药物输送.
科学领域:
- 生物材料科学 生物材料科学
- 药理动力学 药理动力学
- 药物输送系统 药物输送系统
背景情况:
- 外体反应 (FBR) 可以影响植入物释放药物,但文献发现是相互矛盾的.
- 了解FBR对药物药理动学的慢性影响对于长效的可植入药物输送系统至关重要.
研究的目的:
- 直接调查纤维化封装对长效输送植入物皮下药物释放的影响.
- 评估FBR对小分子 (伊斯拉特拉维尔) 和大蛋白 (IgG) 的药理动力学影响.
主要方法:
- 实体植入物 (PMMA,尼龙,PLA) 用于在老鼠中表征FBR.
- 进行了ex vivo扩散性评估和体内药理动力学研究.
- 组织学分析评估了局部组织反应和血管化.
主要成果:
- 纤维囊的厚度和组成在慢性FBR阶段正常化.
- 活体研究表明,随着时间的推移,这两种分子的扩散性增加.
- 观察到一致的伊斯拉特拉维尔血水平;在急性FBR期间,IgG释放被暂时调节.
结论:
- 慢性纤维化封装不会显著影响稳定状态小分子药物释放.
- 急性FBR可能暂时影响药物输送植入物中较大的分子的释放.
- 局部分娩没有诱导显著的炎症或改变血管化.
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