Theranostics 2022; 12(4):1769-1782. doi:10.7150/thno.68456 This issue Cite

Research Paper

A super-stable homogeneous Lipiodol-hydrophilic chemodrug formulation for treatment of hepatocellular carcinoma

Pan He1,2,#, En Ren1,#, Biaoqi Chen3,#, Hu Chen1,#, Hongwei Cheng1, Xing Gao1, Xiaoliu Liang1, Hao Liu3, Jingdong Li5, Bo Li6, Aizheng Chen3, Chengchao Chu1,4, Xiaoyuan Chen7, Jingsong Mao1,2✉, Yang Zhang1✉, Gang Liu1✉

1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.
2. Department of Radiology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, China.
3. Fujian Provincial Key Laboratory of Biochemical Technology, Institute of Biomaterials and Tissue Engineering, Huaqiao University, Xiamen 361021, China.
4. Amoy Hopeful Biotechnology Co., Ltd., Xiamen 361027, China.
5. Department of General Surgery, Institute of Hepatobiliary-Pancreatic-Intestinal Diseases, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.
6. Department of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
7. Departments of Diagnostic Radiology, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore, Singapore.
# P. He, E. Ren, B. Chen, and H. Chen contributed equally to this work.

Citation:
He P, Ren E, Chen B, Chen H, Cheng H, Gao X, Liang X, Liu H, Li J, Li B, Chen A, Chu C, Chen X, Mao J, Zhang Y, Liu G. A super-stable homogeneous Lipiodol-hydrophilic chemodrug formulation for treatment of hepatocellular carcinoma. Theranostics 2022; 12(4):1769-1782. doi:10.7150/thno.68456. https://www.thno.org/v12p1769.htm
Other styles

File import instruction

Abstract

Graphic abstract

Background: Though lipiodol formulations are major options in transcatheter arterial chemoembolization (TACE) of advanced unresectable hepatocellular carcinoma (HCC) in the clinic, their application is severely limited by insufficient physical stability between the hydrophobic lipiodol and hydrophilic drugs; thus, most chemotherapeutic drugs are quickly released into systemic circulation resulting in poor therapeutic outcomes and serious side effects.

Methods: The typical hydrophilic drug doxorubicin hydrochloride (DOX) was prepared as a pure nanomedicine and then stably and homogeneously dispersed in lipiodol (SHIFT&DOX) via slightly ultrasonic dispersion. The drug release profiles of SHIFT&DOX were defined in a decellularized liver model. In vivo therapeutic studies were performed in rat-bearing N1S1 orthotopic HCC models and rabbit-bearing VX2 orthotopic HCC models.

Results: SHIFT&DOX features an ultrahigh homogeneous dispersibility over 21 days, which far surpassed typical Lipiodol-DOX formulations in clinical practice (less than 0.5 h). SHIFT&DOX also has excellent sustained drug release behavior to improve the local drug concentration dependence and increase the time dependence, leading to remarkable embolic and chemotherapeutic efficacy, and eminent safety in all of the orthotopic HCC models.

Conclusions: The carrier-free hydrophilic drug nanoparticle technology-based lipiodol formulation provides a promising approach to solve the problem of drug dispersion in TACE with the potential for a translational pipeline.

Keywords: Hepatocellular carcinoma, Theranostics, Transcatheter arterial chemoembolization, Homogeneous formulation, Embolic agent


Citation styles

APA
He, P., Ren, E., Chen, B., Chen, H., Cheng, H., Gao, X., Liang, X., Liu, H., Li, J., Li, B., Chen, A., Chu, C., Chen, X., Mao, J., Zhang, Y., Liu, G. (2022). A super-stable homogeneous Lipiodol-hydrophilic chemodrug formulation for treatment of hepatocellular carcinoma. Theranostics, 12(4), 1769-1782. https://doi.org/10.7150/thno.68456.

ACS
He, P.; Ren, E.; Chen, B.; Chen, H.; Cheng, H.; Gao, X.; Liang, X.; Liu, H.; Li, J.; Li, B.; Chen, A.; Chu, C.; Chen, X.; Mao, J.; Zhang, Y.; Liu, G. A super-stable homogeneous Lipiodol-hydrophilic chemodrug formulation for treatment of hepatocellular carcinoma. Theranostics 2022, 12 (4), 1769-1782. DOI: 10.7150/thno.68456.

NLM
He P, Ren E, Chen B, Chen H, Cheng H, Gao X, Liang X, Liu H, Li J, Li B, Chen A, Chu C, Chen X, Mao J, Zhang Y, Liu G. A super-stable homogeneous Lipiodol-hydrophilic chemodrug formulation for treatment of hepatocellular carcinoma. Theranostics 2022; 12(4):1769-1782. doi:10.7150/thno.68456. https://www.thno.org/v12p1769.htm

CSE
He P, Ren E, Chen B, Chen H, Cheng H, Gao X, Liang X, Liu H, Li J, Li B, Chen A, Chu C, Chen X, Mao J, Zhang Y, Liu G. 2022. A super-stable homogeneous Lipiodol-hydrophilic chemodrug formulation for treatment of hepatocellular carcinoma. Theranostics. 12(4):1769-1782.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image