Enhancing the therapeutic potential of isoliensinine for hypertension through PEG-PLGA nanoparticle delivery: A comprehensive in vivo and in vitro study

作者：Mengying Yao, Ming‐Fang Wu, Meng Yuan, Meizhu Wu, Aling Shen, Youqin Chen, Dawei Lian, Xiaolong Liu, Jun Peng · 发表于：Biomedicine & Pharmacotherapy · 年份：2024 · DOI：10.1016/j.biopha.2024.116541 · 被引用次数：18 · 研究领域：Chromatography in Natural Products、Computational Drug Discovery Methods、Berberine and alkaloids research

BACKGROUND: Hypertension, a highly prevalent chronic disease, is known to inflict severe damage upon blood vessels. In our previous study, isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), exhibits antihypertensive and vascular smooth muscle proliferation-inhibiting effects, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare isoliensinine loaded by PEG-PLGA polymer nanoparticles to increase its efficacy METHOD: We synthesized and thoroughly characterized PEG-PLGA nanoparticles loaded with isoliensinine using a nanoprecipitation method, denoted as, PEG-PLGA@Isoliensinine. Additionally, we conducted comprehensive investigations into the stability of PEG-PLGA@Isoliensinine, in vitro drug release profiles, and in vivo pharmacokinetics. Furthermore, we assessed the antihypertensive efficacy of this nano-system through in vitro experiments on A7R5 cells and in vivo studies using AngII-induced mice. RESULT: The findings reveal that PEG-PLGA@Isoliensinine significantly improves isoliensinine absorption by A7R5 cells and enhances targeted in vivo distribution. This translates to a more effective reduction of AngII-induced hypertension and vascular smooth muscle proliferation. CONCLUSION: In this study, we successfully prepared PEG-PLGA@Isoliensinine by nano-precipitation, and we confirmed that PEG-PLGA@Isoliensinine surpasses free isoli...