期刊
MOLECULES
卷 28, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/molecules28104147
关键词
acetaminophen; chitosan oligosaccharide; drug-induced liver injury; glycyrrhetinic acid modification; mesoporous silica
The aim of this study was to find a suitable treatment for acute drug-induced liver injury. The use of nanocarriers improved the therapeutic effect of natural drugs in hepatocytes. Dendritic mesoporous silica nanospheres (MSNs) were synthesized and modified with glycyrrhetinic acid (GA) to form drug-loaded nanoparticles (COSM@MSN-NH2-GA). The nano-drug particles enhanced cell uptake and decreased AST and ALT indexes. This study provides a potential nano-delivery scheme for targeted therapy of acute drug-induced liver injury.
Objective: the study was to find a suitable treatment for acute drug-induced liver injury. The use of nanocarriers can improve the therapeutic effect of natural drugs by targeting hepatocytes and higher loads. Methods: firstly, uniformly dispersed three-dimensional dendritic mesoporous silica nanospheres (MSNs) were synthesized. Glycyrrhetinic acid (GA) was covalently modified on MSN surfaces through amide bond and then loaded with COSM to form drug-loaded nanoparticles (COSM@MSN-NH2-GA). The constructed drug-loaded nano-delivery system was determined by characterization analysis. Finally, the effect of nano-drug particles on cell viability was evaluated and the cell uptake in vitro was observed. Results: GA was successfully modified to obtain the spherical nano-carrier MSN-NH2-GA (<= 200 nm). The neutral surface charge improves its biocompatibility. MSN-NH2-GA has high drug loading (28.36% +/- 1.00) because of its suitable specific surface area and pore volume. In vitro cell experiments showed that COSM@MSN-NH2-GA significantly enhanced the uptake of liver cells (LO2) and decreased the AST and ALT indexes. Conclusion: this study demonstrated for the first time that formulation and delivery schemes using natural drug COSM and nanocarrier MSN have a protective effect on APAP-induced hepatocyte injury. This result provides a potential nano-delivery scheme for the targeted therapy of acute drug-induced liver injury.
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