BioJect:一个体外平台,用于探索皮下药物输送中的类的释放动态
David Li1, Qiuhua Qin1, Ayça Altay Benetti1
1Department of Pharmacy and Pharmaceutical Sciences, National University of Singapore, Singapore.
概括
一种新的BioJect细胞方法通过模拟身体的环境,准确地预测皮下药物释放. 它确定了影响胰岛素糖氨酸释放的新型专蛋白结合,改善了配方开发.
科学领域:
- 药理动力学和药物输送方法
- 生物材料和组织工程
- 分析化学 分析化学
背景情况:
- 预测皮下 (SC) 药物释放是复杂的,因为药物特性和生理微环境的相互作用,包括细胞外基质 (ECM),液体组成和可用性.
- 该ECM作为一个过器,受当地离子和蛋白质含量的影响,影响药物的生物可用性和吸收.
- 目前的方法很难完全复制SC环境的复杂性,以准确地预测释放.
研究的目的:
- 引入和验证BioJect细胞,一种用于皮下药物配方的新型释放测试方法.
- 系统地研究四种不同的胰岛素配方的释放机制.
- 在生物相关条件下评估BioJect细胞的生物预测能力.
主要方法:
- 开发BioJect细胞,集成 perfusion 系统与基于综合流通细胞的可定制生物矩阵组件.
- 系统地研究了四种胰岛素配方 (常规人体胰岛素,胰岛素阿斯巴特,胰岛素谷氨酸,NPH胰岛素),使用改性模拟皮下间歇液 (mSSIF).
- 将氨酸和原等生物相关成分纳入BioJect细胞的生物基质中,以模拟SC环境.
主要成果:
- 在不同的生物相关条件下,BioJect细胞方法成功地区分了测试的胰岛素配方,证明了生物预测潜力.
- 发现了一种以前未经记录的对白蛋白结合的相互作用,影响了胰岛素糖氨酸的释放速度,这与SC低剪切环境特异.
- 包括ECM组件提供了对药物吸收和释放的见解,得到了体外和体内相关性 (C级和A级) 的支持.
结论:
- 在药物释放测试中,BioJect细胞是模拟SC环境的重大进步.
- 考虑蛋白质结合和ECM成分对于准确预测SC配方药物吸收至关重要.
- 这种方法为优化皮下药物递送系统的开发提供了一个有前途的工具.
关键词:
ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME ADME吸收方式 吸收方式生物预测性生物预测性生物相关的生物相关性扩散试验 扩散试验解散 解散 解散 是一个过程.药物释放测定 药物释放测定IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC IVIVC在体外-体内关系 (IVIVR)非口服复合药物 非口服复合药物酸是一种酸.性能测试 性能测试 性能测试在皮下 (SC)
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