药物输送和兼容性研究的方法在一个被粘液覆盖的ex vivoCaco-2细胞单层模型中
Janni S Mortensen1, Freja Bohr1, Emilie E M Nielsen2
1Center for Biopharmaceuticals and Biobarriers in Drug Delivery (BioDelivery), Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark; Department of Chemistry, Nano-Science Center, Center for Optimised Oligo Escape and Control of Disease Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, DK-1870 Frederiksberg, Denmark.
International journal of pharmaceutics
|June 29, 2025
概括
研究人员使用ex vivo猪肠粘液开发了一种更具生物相关性的Caco-2细胞模型. 这种先进的模型更好地模仿本地肠道屏障,改善了口服药物输送研究.
科学领域:
- 生物制药生物制药公司
- 细胞生物学 细胞生物学
- 药物运输 药物运输 药物运输
背景情况:
- 可可-2细胞单层被广泛用于口服药物输送研究.
- 试管粘液模型往往无法准确地模仿本地粘液的特性.
- 需要一个更具生物相关性的模型来提高口服药物输送研究的稳定性.
研究的目的:
- 使用ex vivo猪肠粘液开发一种更具生物相关性的Caco-2细胞模型.
- 为了评估猪肠粘液 (HYP-PIM和ISO-PIM) 与Caco-2细胞的高位和同位ex vivo生物相容性.
- 评估口服药物输送新模式的屏障特性.
主要方法:
- 在Caco-2细胞单层上覆盖了HYP-PIM和ISO-PIM.
- 生物相容性是通过基底侧活力测定,体电阻 (TEER) 测量和核形态学来评估的.
- 通过测量环素A的透度来评估屏障功能.
主要成果:
- HYP-PIM和ISO-PIM被Caco-2细胞单层承受得很好,由直角生物相容性试验证实.
- 猪肠粘液的ex vivo模型显示了对环素A透的显著屏障特性.
- 与猪胃粘素 (PGMII) 相比,HYP-PIM和ISO-PIM显示出优越的屏障功能.
结论:
- 原生猪肠粘液 (HYP-PIM和ISO-PIM) 为Caco-2细胞模型提供了更具生物相关性的覆盖.
- 这种增强的模型精确地模仿了本地肠道屏障,为口服药物输送提供了更好的洞察力.
- 开发的模型代表了与目前用于药物透性研究的体外粘液替代品相比的显著进步.
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