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

Xiaochuan Tan; Yumei Hao; Nai Ma; Yige Yang; Wenzhen Jin; Ya Meng; Chuchu Zhou; Wensheng Zheng; Yujia Zhang

doi:10.1080/10717544.2023.2219432

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

Drug Deliv. 2023 Dec;30(1):2219432. doi: 10.1080/10717544.2023.2219432.

Authors

Xiaochuan Tan¹, Yumei Hao¹, Nai Ma¹, Yige Yang¹, Wenzhen Jin¹, Ya Meng¹, Chuchu Zhou¹, Wensheng Zheng¹, Yujia Zhang¹

Affiliation

¹ Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

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; M6P-HSA-MT-SLN; matrine; target delivery.

MeSH terms

Humans
Liposomes
Liver Cirrhosis / metabolism
Matrines*
Nanoparticles*

Substances

Lipid Nanoparticles
Matrines
Liposomes

Grants and 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.