通过一个多孔的微球-凝复合系统,改善PLGA微球中利拉格卢提德的释放
Lei Liu1, Mingxiu Zheng1, Rongcai Liang1,2
1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation(Yantai University), Ministry of Education, Yantai University, Yantai, People's Republic of China.
Pharmaceutical development and technology
|March 11, 2024
概括
这项研究开发了一种新的多孔微球-凝复合物,用于持续释放利拉古. 该系统显著减少了最初的药物释放,并在体内延长了治疗效果.
科学领域:
- 生物材料科学 生物材料科学
- 药物输送系统 药物输送系统
- 聚合物化学 聚合物化学
背景情况:
- 利拉格卢提德是一种类似葡萄糖类-1受体激动剂,需要有效的输送系统来持续治疗作用.
- 基于微球的药物递送提供了可控释放的潜力,但通常面临着初始突发释放和短时间的挑战.
- 将微球与刺激响应凝结合在一起的复合系统可以增强药物释放概况.
研究的目的:
- 开发和表征一种新型的,含有利拉格卢提德的多孔微球-凝复合系统.
- 评估复合系统在体外和体内持续释放药物的性能.
- 调查聚乙烯糖醇 (PEG) 度对药物释放动力学的影响.
主要方法:
- 用聚乙烯糖醇 (PEG) 作为菌剂制备充满利拉格卢提德的多孔聚 (乳糖-co-糖酸) (PLGA) 微球.
- 在一个温度敏感的凝矩阵中分散含有利拉格卢提德的微球,该矩阵由波洛克萨默407 (F-127) 和波洛克萨默188 (F-68) 组成.
- 在小鼠体内药物释放研究和体内药物动力学评估.
主要成果:
- 毛孔微球-凝复合系统显著减少了最初的药物释放 (1天内4.7%).
- 在微球中增加PEG度将快速释放阶段的药物释放率从53%降低到29%,从而减缓释放率.
- 在体内研究表明,释放时间延长了大约10天,减少了最初的突发释放,减少了血液中药物度波动 (AUC0-1降低了24.78 ng/ml*h).
结论:
- 开发的多孔微球-凝复合体系统为持续和长期的利拉格卢提德输送提供了一个有前途的平台.
- 复合基质的合理设计,特别是孔形成剂度,有效控制药物释放动力学.
- 这种方法为开发具有改善药物动力学特征的先进药物递送系统提供了一种新的策略.
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