Preparation of glycyrrhizic acid functionalized nanostructured lipid carrier loaded with tanshinone IIA and its anti-hepatic fibrosis effect.

In this study, the natural active ingredient glycyrrhizic acid (GA) was used to replace traditional synthetic surfactants to construct GA-functionalized Tanshinone IIA (TSA) nanostructured lipid carriers (TSA@GA NLCs). The prepared TSA@GA NLCs had a particle size of 268.7 ± 2.3 nm and an encapsulation efficiency of 84.90 ± 5.45%. They exhibited a spherical core-shell structure, demonstrated good preliminary short-term stability, and displayed in vitro release profiles consistent with those of an oral sustained-release delivery system. In a carbon tetrachloride (CCl4)-induced mouse model of liver fibrosis, TSA@GA NLCs significantly reduced serum transaminase levels (ALT decreased from 246.90 ± 9.73 U/L in the model group to 83.82 ± 2.87 U/L, AST from 348.77 ± 7.66 U/L to 139.87 ± 4.31 U/L), and reversed levels of inflammatory factors (TNF-α from 62.57 ± 1.33 μg/L to 18.83 ± 0.73 pg/mL; IL-1β and IL-6 showed consistent trends) and oxidative stress markers (MDA decreased from 1.88 ± 0.11 nmol/mg prot to 1.25 ± 0.03 nmol/mg prot, GSH increased from 11.36 ± 0.49 nmol/mg prot to 14.70 ± 1.00 nmol/mg prot), improved histopathological damage to liver tissue, reduced collagen deposition, and suppressed α-SMA expression. The TSA@GA NLCs group demonstrated significantly better improvement across all indicators. Furthermore, this study preliminarily investigated changes in protein expression in the NRF2/NF-κB pathway; however, molecular interactions between these pathways require further validation. The findings indicate that GA possesses dual functions of structural stabilization and combination-enhanced therapy. Through an integrated "delivery-therapy" strategy, TSA@GA NLCs effectively enhanced the antifibrotic efficacy of TSA, providing new insights for the design of delivery systems for active ingredients in traditional Chinese medicine.