Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 81, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2023.104274
Keywords
Curcumae rhizoma exosomes-like nanoparticles; Astragalus components; Uptake; Transport; Antitumor activity; Pharmacokinetics
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This study aimed to improve the absorption of Astragalus components (AC) using plant exosomes and demonstrate the synergistic mechanism of AC-loaded Curcumae Rhizoma Exosomes-like nanoparticles (AC-CELNs). CELNs containing active ingredients from Curcumae Rhizoma were extracted and loaded with Formononetin, Astragaloside IV, and Calycosin from Astragalus. AC-CELNs showed slow drug release and improved stability against gastric and intestinal fluids. They also exhibited superior uptake and transport capacity in cell models, and the endocytosis pathways involved clathrin- and caveolin-dependent mechanisms. AC-CELNs significantly decreased cell survival in a time- and concentration-dependent manner. Additionally, pharmacokinetic studies in rats showed that CELNs promoted the in vivo absorption of AC. These findings suggest that CELNs are promising carriers for enhancing the absorption and anti-tumor activity of AC.
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.
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