固体自我微乳化药物输送系统,以改善雷卢戈利克斯的口服生物可用性:制备和评估
Zi-Lin Li1, Guo-Xing Deng1, Chuan-Zhou Fang1
1School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People's Republic of China.
International journal of nanomedicine
|January 31, 2025
概括
固体自我微乳化药物输送系统 (S-SMEDDS) 显著增强了口服里卢戈力克斯 (RLGL) 的吸收. 这种新的配方提高了生物可用性,并没有显著的毒性,为难溶性药物提供了有前途的输送方法.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 生物制药生物制药公司
背景情况:
- 雷卢戈力克斯 (RLGL) 由于溶解度低和P-葡萄糖蛋白 (P-gp) 排泄而表现出较差的口服生物利用性.
- 有效的药物输送系统对于改善吸收不良药物的治疗疗效至关重要.
- 自行微乳化药物输送系统 (SMEDDS) 具有提高口服吸收的潜力.
研究的目的:
- 开发和评估一种固体的自我微乳化药物输送系统 (RLGL-S-SMEDDS),以改善relugolix的口服吸收.
- 调查优化RLGL-S-SMEDDS配方的体外和体内性能.
- 评估S-SMEDDS在克服P-gp介导药物外流和增强药物透方面的潜力.
主要方法:
- 使用可溶性研究和伪三次相图来优化SMEDDS的配方,然后进行设计专家优化.
- RLGL-S-SMEDDS的表征,包括粒子大小,泽塔潜力,形态和热力学稳定性.
- 在体外释放药物,Caco-2细胞运输研究,以及在动物模型中的体内药理动力学和毒理学评估.
主要成果:
- 优化的RLGL-S-SMEDDS配方在体外显著增强了药物释放 (86%对3.6%的悬浮).
- 实验室研究显示,Caco-2细胞吸收增加了三倍,并表明淋巴吸收和P-gp抑制.
- 与RLGL悬浮剂相比,体内研究显示RLGL-S-SMEDDS口服生物利用率增加了1.9倍,没有观察到毒性.
结论:
- 固体自我微乳化药物输送系统 (S-SMEDDS) 是一种安全有效的策略,可以提高relugolix的口服吸收.
- 这种方法具有显著的潜力,可以改善具有较差生物可用性和P-gp基质特征的药物的口服输送.
- 开发的RLGL-S-SMEDDS配方为口服Relugolix提供了一个可行的替代方案,改善了其治疗指数.
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