M6P-modified solid lipid nanoparticles loaded with matrine for the treatment of fibrotic liver

Abstract

Liver fibrosis is a key pathological process shared by the progression of various chronic liver diseases. Treatment of liver fibrosis can effectively block the occurrence and development of hepatic cirrhosis or even carcinoma. Currently, there is no effective drug delivery vehicle for curing liver fibrosis. In this study, we designed matrine (MT)-loaded mannose 6-phosphate (M6P) modified human serum albumin (HSA) conjugated solid lipid nanoparticles (SLN), named M6P-HSA-MT-SLN for treatment of hepatic fibrosis. We demonstrated that M6P-HSA-MT-SLN exhibited controlled and sustained release properties and good stability over 7 days. The drug release experiments showed that M6P-HSA-MT-SLN exhibited slow and controlled drug release characteristics. In addition, M6P-HSA-MT-SLN showed a significant targeted ability to fibrotic liver. Importantly, in vivo studies indicated that M6P-HSA-MT-SLN could significantly improve histopathological morphology and inhibit the fibrotic phenotype. In addition, in vivo experiments demonstrate that M6P-HSA-MT-SLN could reduce the expression of fibrosis markers and alleviate the damage of liver structure. Hence, the M6P-HSA-MT-SLN provide a promising strategy to deliver therapeutic agents to fibrotic liver to prevent liver fibrosis.

Keywords:

• Liver fibrosis
• matrine
• M6P-HSA-MT-SLN
• target delivery

Author contributions

Wensheng Zheng and Yujia Zhang designed the overall project. Xiaochuan Tan mainly carried out all the experiments and wrote the manuscript. Yumei Hao wrote the manuscript and carried out some related experiment. Other authors, such as Nai Ma, Yige Yang, Wenzhen Jin, Ya Meng, Chuchu Zhou participated in some related experiment.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethical approval statement

The authors have adhered to the ARRIVE guidelines. All animal procedures were performed in accordance with the guidelines approved by the Animal Care and Use Committee of the National Institutes for Food and Drug Control (No. 2019 (B) 011) and Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (No. 00007661). Except for the C57 mice and SD rat used in this experiment, other animals cannot effectively construct models and evaluate pharmacodynamics. All animals were housed at 22 ± 1 °C, relative humidity 50 ± 1%, and a light/dark cycle of 12/12 h. All rats and mice had free access to food and water. Mice were euthanized by intraperitoneal injection of excessive pentobarbital sodium.

Additional information

Funding

This work was supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-028) and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine (202105AG070012). All animal procedures were carried out under the guidelines approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College.