Abstract
Liver fibrosis remains a significant public health problem. However, few drugs have yet been validated. Costunolide (COS), as a monomeric component of the traditional Chinese medicinal herb Saussurea Lappa, has shown excellent anti-fibrotic efficacy. However, COS displays very poor aqueous solubility and poor stability in gastric juice, which greatly limits its application via an oral administration. To increase the stability, improve the dissolution rate and enhance the anti-liver fibrosis of COS, pH-responsive mesoporous silica nanoparticles (MSNs) were selected as a drug carrier. Methacrylic acid copolymer (MAC) as a pH-sensitive material was used to coat the surface of MSNs. The drug release behavior and anti-liver fibrosis effects of MSNs-COS-MAC were evaluated. The results showed that MSNs-COS-MAC prevented a release in the gastric fluid and enhanced the dissolution rate of COS in the intestinal juice. At half the dose of COS, MSNs-COS-MAC still effectively ameliorated parenchymal necrosis, bile duct proliferation and excessive collagen. MSNs-COS-MAC significantly repressed hepatic fibrogenesis by decreasing the expression of hepatic fibrogenic markers in LX-2 cells and liver tissue. These results suggest that MSNs-COS-MAC shows great promise for anti-liver fibrosis treatment.
Highlights
Liver fibrosis is an ultimate pathological feature of all forms of chronic hepatic damage.Progressive fibrosis often results in cirrhosis, which is responsible for significant morbidity and mortality worldwide [1,2,3]
The transmission electron microscopy (TEM) images showed that the mean pore sizes of mesoporous silica nanoparticles (MSNs) were about 10 nm and the pore channels were clearly visible (Figure 1A)
At a 187 half dose of COS, MSNs-COS-Methacrylic acid copolymer Type A (MAC) showed a stronger anti-fibrotic effect. These findings half dose of COS, MSNs-COS-MAC showed a stronger anti-fibrotic effect. These findings indicate that MSNs-COS-MAC could inhibit the progression of fibrosis more effectively indicate that MSNs-COS-MAC could inhibit the progression of fibrosis more effectively than COS in Bile Duct Ligation (BDL) rats
Summary
Liver fibrosis is an ultimate pathological feature of all forms of chronic hepatic damage. Costunolide as a sesquiterpene lactone displays very poor aqueous solubility and poor stability in gastric juice, which greatly limits its application via an oral administration [18,19] To overcome these drawbacks of COS, a suitable oral delivery system is of. 2 o solubility and poor stability in gastric juice, which greatly limits its application via an o administration [18,19] To overcome these drawbacks of COS, a suitable oral delivery s tem is of great necessity to improve its waterin solubility and stability in gastric juice, t great necessity to improve its water solubility and stability gastric juice, enhancing enhancing the anti-liver fibrosis effect. The in vivo anti-fibrotic effect on rats was evaluated by testing liver histology, cells. By testing liver histology, hepatic patic functionseffect and the of profibrotic functions and the level of profibrotic mediators
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