Curcumae Rhizoma Exosomes-like nanoparticles loaded Astragalus components improve the absorption and enhance anti-tumor effect

Aimed to improve the absorption of Astragalus components (AC) via plant exosomes and demonstrate the synergistic mechanism of AC-loaded Curcumae Rhizoma Exosomes-like nanoparticles (AC-CELNs). CELNs with Curcumae Rhizoma active ingredients were extracted from the Curcumae Rhizoma by sucrose density gradient centrifugation method, and Formononetin, Astragaloside IV and Calycosin from Astragalus were loaded in CELNs by ultrasonic. AC-CELNs showed slow drug release in PBS (pH 7.4) compare to free AC, and encapsulation into CELNs helped to stabilize AC against simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). In addition, AC-CELNs exhibited superior uptake and transmembrane transport capacity on Caco-2 cell models and the endocytosis pathways related to the clathrin- and caveolin-dependent endocytosis (P < 0.001 vs. free AC). MTT assay showed that AC-CELNs decreased the survival rate significantly against Caco-2 cells (42.58% at 48 h) and HeLa cells (33.34% at 48 h), and the inhibition was time-dependent and concentration-dependent. Furthermore, the pharmacokinetic parameters of Formononetin, Astragaloside IV, and Calycosin in rat plasma showed that CELNs could better promote the in vivo absorption of AC (P < 0.05). The present study proposes that the CELNs are the potential and promising carriers to promote the absorption of AC in vitro or in vivo, and the combination of AC and CELNs is available for the enhancement of synergistic anti-tumor activity.