克服胃肠道粘液屏障:依赖调节粘酶活性
Padryk Merkl1, Ivana Vukšinić1, Corey Archer2
1Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich 8093 Zurich, Switzerland.
International journal of pharmaceutics
|December 1, 2025
概括
口服治疗药物面临着粘液屏障的挑战. 细菌酶StcE显示出潜力,但它的有效性各不相同. 补充剂可以增强StcE.
科学领域:
- 生物化学 生物化学
- 药物运输 药物运输 药物运输
- 胃肠病学 胃肠病学
背景情况:
- 口服是治疗目的的首选,但由于胃肠道障碍而受到阻碍.
- 由粘膜组成的肠粘液层是一个重要的,但经常被忽视的障碍.
- 细菌粘酶,如StcE (C1酶抑制剂的分泌蛋白酶),可以降解粘液.
研究的目的:
- 为了调查StcE的粘菌解毒功效中个体间变异的原因.
- 评估粘液暴露后StcE的结构完整性和活性.
- 确定可用性在限制StcE功能中的作用.
主要方法:
- 使用质谱法,PAGE和体外测试来评估酶完整性和活性.
- 使用ICP-MS. 在粘液中的量化总和非蛋白质结合的.
- 评估了补充剂对StcE粘合效率的影响.
主要成果:
- 在粘液暴露后,StcE在结构上保持完整和功能.
- 粘液中非蛋白质结合的低水平表明潜在的限制.
- 补充剂显著提高了StcE的粘合效率.
结论:
- 由于粘液中的可用性有限,StcE疗效的变化很可能是由于粘液中的可用性有限.
- 结合补充剂的StcE显示出降低粘液屏障的潜力.
- 这一战略需要进一步研究,以改善复杂治疗药物的口服输送.
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