Affiliation:
1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
2. Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, China
3. Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27514, USA
Abstract
Background:
Liver fibrosis usually progresses to liver cirrhosis and even results in hepatocellular
carcinoma, which accounts for one million deaths annually worldwide. To date, anti-liver fibrosis
drugs for clinical treatment have not yet been approved. Nowadays, as a natural regulator, Relaxin
(RLX) has received increased attention because the expression of RLX could deactivate the activation
of hepatic stellate cells (aHSCs) and resolve liver fibrosis. However, its application in treatment is limited
due to the short half-life in circulation and low accumulation within the target organ.
Methods:
To address these problems, a kind of polymeric metformin (PolyMet)-loaded relaxin plasmid
(pRLX) core-membrane lipid nanoparticle (PolyMet-pRLX-LNPs, PRLNP) was prepared. Here,
PolyMet was used as a carrier to replace the traditional polymer polyethylene diene (PEI), which is of
higher toxicity, to prolong the circulation time of pRLX in vivo. Then, the antifibrotic ability of PRLNP
to overcome liver fibrosis was carried out in C57BL/6 mice. It is worth mentioning that this is the first
time to investigate the potential of PRLNP in carbon tetrachloride-induced liver fibrosis.
Results:
The results showed that PRLNP effectively downregulated fibrosis-related biomarkers such as
alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, histopathological
examinations also showed low collagen accumulation, revealing that PRLNP could histologically and
functionally alleviate liver fibrosis. In addition, no significant difference in serum biochemical value
between the PRLNP and the normal group, suggesting the safety profile of PRLNP.
Conclusion:
This research proposed a novel non-toxic treatment method for liver fibrosis with a nanosystem
to effectively treat liver fibrosis.
Funder
Health Bureau of Zhejiang Province
National College Students' innovation and entrepreneurship training program
Publisher
Bentham Science Publishers Ltd.
Cited by
1 articles.
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