透性基准测试:用于比较,玻璃和活体测量的指南
Christian Jorgensen1,2, Raleigh M Linville3, Ian Galea4
1School of Medicine, Pharmacy and Biomedical Sciences, Faculty of Science & Health, University of Portsmouth, Portsmouth PO1 2DT, Hampshire, U.K.
Journal of chemical information and modeling
|January 17, 2025
概括
这项研究提供了指导方针,用于在计算,体外和体外方法中对细胞透性数据进行基准测试. 准确的透性测量对于药物输送和了解疾病至关重要.
科学领域:
- 药理学 药理学是指药理学的学科.
- 生物物理学的生物物理.
- 计算生物学 计算生物学
背景情况:
- 透性量化了跨越生物障碍的分子运输,这对于药物输送和疾病建模至关重要.
- 准确的透率数据 (cm/s) 对于正常生理功能和病理条件都至关重要.
- 血脑屏障 (BBB) 对治疗剂进入大脑提出了重大挑战.
研究的目的:
- 建立社区主导的指导方针,用于在各种方法和生物环境中对透性数据进行基准测试.
- 为调整模拟数据与实验分析提供一个框架,以提高准确性和可靠性.
- 优化透性测试,以促进药物输送研究和开发.
主要方法:
- 介绍了三种透性计算方法的分析框架:in silico (基于过渡的计数,不均质可溶性扩散),in vitro (2D/3D细胞培养) 和in vivo (in situ脑 perfusion,多个时间点回归).
- 证明了对in silico方法与in vitro和in vivo测定进行系统的比较.
- 讨论了测试设计选择及其对基准测试结果的影响.
主要成果:
- 基准测试揭示了结果对特定测试设计参数的敏感性.
- 识别了调和计算预测与实验透性数据的挑战.
- 强调了组织特异性考虑的重要性,例如血脑屏障.
结论:
- 为提高数据可靠性,建议用于透性基准测试的七种最佳实践.
- 强调量身定制的透性测试对于成功的药物输送研发的重要性.
- 旨在提高用于治疗应用的透性建模的准确性和一致性.
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