Dual-ligand-functionalized nanostructured lipid carriers as a novel dehydrocavidine delivery system for liver fibrosis therapy.

Colloids Surf B Biointerfaces

Department of Pharmacy, Guangxi Medical University, Nanning 530021, China; Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Nanning 530021, China; Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, Nanning 530021, China. Electronic address:

Published: February 2025

Background: Liver fibrosis is a common stage of various chronic liver diseases, often developing into liver cirrhosis, and even liver cancer. Activated hepatic stellate cells (aHSCs) have been shown to promote the development of liver fibrosis. Therefore, dual-targeted combination therapy for liver may be an effective strategy for the treatment of liver fibrosis.

Purpose: In this study, the novel nanostructured lipid carriers (GA&GalNH-DC-NLCs) were prepared for Dehydrocavidine (DC), glycyrrhetinic acid (GA) and galactose-PEG-NH (GalNH) were selected as targeted ligand-modified nanostructured lipid carriers (NLCs), which enables dual-targeting to the liver for the treatment of liver fibrosis.

Study Design: To study the targeting effect of GA&GalNH-DC-NLCs on liver and its therapeutic effect on liver fibrosis, we established aHSC-T6 cell model and rat model of liver fibrosis for study.

Results: GA&GalNH-DC-NLCs promoted drug liver targeting efficiency and apoptosis rate by upregulating the expression of Bax. It showed that compared with no and/or GA-modified NLCs and GalNH-modified NLCs, GA&GalNH-DC-NLCs exhibited less extracellular matrix (ECM) deposition, induced apoptosis of aHSCs, and stronger anti-fibrosis effects in vivo. This may be due the fact that GA or GalNH-modifified NLCs simultaneously block HSCs activation and inhibit the IL-6/STAT3 pathway.

Conclusion: GA&GalNH-DC-NLCs is thus a potential strategy for liver fibrosis treatment.

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http://dx.doi.org/10.1016/j.colsurfb.2024.114376DOI Listing

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