通过ER-Golgi通路通过脂友复合体通过肠球细胞增强普罗利德的透
Jia Meng1, May Yee Chan1, Cheng Peng1
1School of Pharmaceutical Sciences, Beijing Frontier Research Center for Biological Structure, and Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, PR China.
概括
开发口服类药物面临着降解和吸收不良等挑战. 这项研究通过通过ER-Golgi通路引导烯化物 (LEU),改善淋巴吸收并可能减少肝脏代谢,从而增强口服类药物输送.
科学领域:
- 制药科学 制药科学
- 药物运输 药物运输 药物运输
- 生物技术是生物技术.
背景情况:
- 类药物的口服输送受到胃肠道降解和低生物利用度的阻碍.
- 类药物面临酶分解和通过肠道屏障的吸收不良.
- 淋巴吸收提供了一种潜在的途径,可以绕过肝脏的第一通代谢和 lysosomal 降解.
研究的目的:
- 通过促进淋巴吸收来提高类药物的口服生物可用性.
- 调查一项策略,以转移细胞内贩运的烯化物 (LEU) 进入ER-Golgi通路.
- 评估脂友复合和口服乳液配方对LEU吸收的影响.
主要方法:
- 用脂友复合物 (LEU) 与脂友辅助剂配制普罗化的脂友复合物.
- 开发一种含有LEU复合物的口服乳液.
- 在Caco-2细胞单层模型中评估LEU透率.
- 分析LEU吸收途径,包括通过介质淋巴结 (MLN) 进行淋巴运输.
主要成果:
- 通过Caco-2细胞透的LEU从内体-解体通路被转移.
- 低氨被通过中腔淋巴结 (MLN) 吸收到血液中.
- 脂性LEU复合物改善了肠细胞的通透性,并绕过了 lysosomal 降解.
结论:
- 开发的策略增强了类药物的淋巴吸收.
- 将LEU转移到ER-Golgi通路可以改善口服生物可用性.
- 这种方法可能会减少口服治疗的第一通肝新陈代谢.
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