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从分子到吸收:一种多尺度的框架,用于皮下生物输送
Mario de Lucio1, Vivek Sree1, Galen Shi1
1Eli Lilly and Company, Indianapolis, IN, USA.
Advanced drug delivery reviews
|March 13, 2026
概括
单克隆抗体 (mAbs) 的皮下注射面临着由于合药物,设备和组织相互作用的挑战. 药物-设备-容器-组织框架揭示了交叉接口动态作为优化交付的关键.
科学领域:
- 生物制药配方和输送科学.
- 生物材料和药物输送工程.
- 药理动力学和药物吸收.
背景情况:
- 皮下注射 (SC) 首选用于自我注射的单克隆抗体 (mAbs).
- 由于跨尺度的复杂相互作用,一致的生物利用性具有挑战性.
- 优化单个组件只能带来有限的改进.
研究的目的:
- 引入药物-设备-容器-组织 (DDCT) 框架,以实现统一的多尺度分析.
- 追踪mAbs从储存到注射到淋巴吸收的过程.
- 确定优化SC交付的关键瓶.
主要方法:
- 综合分子动力学模拟的发现.
- 采用风湿学测量和高速成像.
- 采用孔机械建模来进行组织反应分析.
主要成果:
- 抗体自我关联影响粘度,扩散,可注射性和组织运输.
- 设备的启动可能会导致不稳定性 (滑动,洞化,剪切);存在缓解策略.
- 注射参数和组织异质性极大地影响输送可靠性和吸收动力学.
结论:
- DDCT框架强调跨界面交互是主要的瓶.
- 这一框架使下一代自动注射器和配方的合理设计成为可能.
- 基于这些多尺度原则,可以开发预测计算工具.
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