背景:高血压,一种非常普遍的慢性疾病,已知会对血管造成严重损害。在我们之前的研究中,异莲心碱,一种二苄基异喹啉生物碱,从一种名为莲花的中药(NelumbonuciferaGaertn)中分离出来,表现出抗高血压和血管平滑肌增殖抑制作用,但是由于水溶性差和生物利用度低,其应用受到限制。在这项研究中,我们提出了制备由PEG-PLGA聚合物纳米粒子负载的异莲心碱,以增加其功效方法:我们合成和彻底表征PEG-PLGA纳米粒子负载的异莲心碱使用纳米沉淀法,表示为,PEG-PLGA@Isoliensinine。此外,我们对PEG-PLGA@Isoliensinine的稳定性进行了全面调查,体外药物释放曲线,和体内药代动力学。此外,我们通过对A7R5细胞的体外实验和使用AngII诱导的小鼠的体内研究,评估了该纳米系统的抗高血压功效.
结果:研究结果表明,PEG-PLGA@Isoliensinine显着改善了A7R5细胞对isoliensinine的吸收,并增强了体内的靶向分布。这意味着更有效地减少AngII诱导的高血压和血管平滑肌增殖。
结论:在这项研究中,我们成功地通过纳米沉淀法制备了PEG-PLGA@Isoliensinine,我们证实PEG-PLGA@Isoliensinine在治疗高血压的有效性方面优于游离的isoliensinine,通过体内和体外实验证明。
结论:本研究为异莲心碱在高血压治疗和血管病变保护方面的临床应用奠定了基础。为提高中药成分的生物利用度提供新的见解。重要的是,没有观察到毒性,肯定了这种创新的药物递送系统在体内的成功实施,并为增强异甘宁的有效性提供了有希望的策略,并提出了开发中药单体新型制剂的创新途径。
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.
RESULTS: 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.
CONCLUSIONS: In this
study, we successfully prepared PEG-PLGA@Isoliensinine by nano-precipitation, and we confirmed that PEG-PLGA@Isoliensinine surpasses free isoliensinine in its effectiveness for the treatment of hypertension, as demonstrated through both in vivo and in vitro experiments.
CONCLUSIONS: This
study lays the foundation for isoliensinine\'s clinical use in hypertension treatment and vascular lesion protection, offering new insights for enhancing the bioavailability of traditional Chinese medicine components. Importantly, no toxicity was observed, affirming the successful implementation of this innovative drug delivery system in vivo and offers a promising strategy for enhancing the effectiveness of Isoliensinine and propose an innovative avenue for developing novel formulations of traditional Chinese medicine monomers.