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

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.

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.

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.

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.