Sequential drug delivery for liver diseases

Xiaozhong Huang; Fan Lee; Yao Teng; Corey Bryen Lingam; Zijian Chen; Min Sun; Ziwei Song; Gowri M Balachander; Hwa Liang Leo; Qiongyu Guo; Imran Shah; Hanry Yu

doi:10.1016/j.addr.2019.11.001

Sequential drug delivery for liver diseases

Adv Drug Deliv Rev. 2019 Sep-Oct:149-150:72-84. doi: 10.1016/j.addr.2019.11.001. Epub 2019 Nov 15.

Authors

Xiaozhong Huang¹, Fan Lee², Yao Teng¹, Corey Bryen Lingam³, Zijian Chen⁴, Min Sun⁵, Ziwei Song¹, Gowri M Balachander⁵, Hwa Liang Leo³, Qiongyu Guo⁶, Imran Shah⁷, Hanry Yu⁸

Affiliations

¹ Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9-04-11, 2 Medical Drive, Singapore 117593, Singapore; Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #06-01, 31 Biopolis Way, Singapore 138669, Singapore.
² Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #06-01, 31 Biopolis Way, Singapore 138669, Singapore.
³ Department of Biomedical Engineering, National University of Singapore, Engineering Drive 3, Engineering Block 4, #04-08, Singapore 117583, Singapore.
⁴ Department of Biomedical Engineering, National University of Singapore, Engineering Drive 3, Engineering Block 4, #04-08, Singapore 117583, Singapore; Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen 518055, China.
⁵ Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9-04-11, 2 Medical Drive, Singapore 117593, Singapore.
⁶ Department of Biomedical Engineering, Southern University of Science and Technology, 1088 Xueyuan Avenue, Shenzhen 518055, China.
⁷ National Center for Computational Toxicology, United States Environmental Protection Agency, 4930 Old Page Rd., Durham, NC 27703, USA.
⁸ Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9-04-11, 2 Medical Drive, Singapore 117593, Singapore; Institute of Bioengineering and Nanotechnology, A*STAR, The Nanos, #06-01, 31 Biopolis Way, Singapore 138669, Singapore; Mechanobiology Institute, National University of Singapore, T-Lab, #05-01, 5A Engineering Drive 1, Singapore 117411, Singapore; CAMP, Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Level 4 Enterprise Wing, Singapore 138602, Singapore; Gastroenterology Department, Southern Medical University, Guangzhou 510515, China. Electronic address: hanry_yu@nuhs.edu.sg.

PMID: 31734169
DOI: 10.1016/j.addr.2019.11.001

Abstract

The liver performs critical physiological functions such as metabolism/detoxification and blood homeostasis/biliary excretion. A high degree of blood access means that a drug's resident time in any cell is relatively short. This short drug exposure to cells requires local sequential delivery of multiple drugs for optimal efficacy, potency, and safety. The high metabolism and excretion of drugs also impose both technical challenges and opportunities to sequential drug delivery. This review provides an overview of the sequential events in liver regeneration and the related liver diseases. Using selected examples of liver cancer, hepatitis B viral infection, fatty liver diseases, and drug-induced liver injury, we highlight efforts made for the sequential delivery of small and macromolecular drugs through different biomaterials, cells, and microdevice-based delivery platforms that allow fast delivery kinetics and rapid drug switching. As this is a nascent area of development, we extrapolate and compare the results with other sequential drug delivery studies to suggest possible application in liver diseases, wherever appropriate.

Keywords: Drug delivery; Liver cancer; Liver regeneration; Microdevice; NASH; TACE.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Drug Delivery Systems*
Hepatitis B / drug therapy*
Hepatitis B / pathology
Humans
Liver Diseases / drug therapy*
Liver Diseases / pathology
Liver Neoplasms / drug therapy*
Liver Neoplasms / pathology