Efficient drug and gene delivery to liver fibrosis: rationale, recent advances, and perspectives

Abstract

Liver fibrosis results from chronic damages together with an accumulation of extracellular matrix, and no specific medical therapy is approved for that until now. Due to liver metabolic capacity for drugs, the fragility of drugs, and the presence of insurmountable physiological obstacles in the way of targeting, the development of efficient drug delivery systems for anti-fibrotics seems vital. We have explored articles with a different perspective on liver fibrosis over the two decades, then collected and summarized the information by providing corresponding in vitro and in vivo cases. We have discussed the mechanism of hepatic fibrogenesis with different ways of fibrosis induction in animals. Furthermore, the critical chemical and herbal anti-fibrotics, biological molecules such as micro-RNAs, siRNAs, and growth factors, which can affect cell division and differentiation, are mentioned. Likewise, drug and gene delivery and therapeutic systems on in vitro and in vivo models are summarized in the data tables. This review article enlightens recent advances in emerging drugs and nanocarriers and represents perspectives on targeting strategies employed in liver fibrosis treatment.

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

“…HSCs are the main source of the ECM and the central link in the occurrence and development of liver fibrosis. 24 Under normal conditions, HSCs account for 5%–15% of all the hepatic cells in the liver and are in a resting state. HSCs are responsible for the metabolism and storage of vitamin A and fat, and the synthesis and secretion of collagen, glycoproteins, MMPs, and TIMPs.…”

Bergenin Attenuates Hepatic Fibrosis by Regulating Autophagy Mediated by the PPAR-γ/TGF-β Pathway

“…Research on liver fibrosis has recently entered a new era. Great progress has been made in understanding liver fibrosis and drug-targeted therapy [ 1 , 25 ]. Natural plant extracts have been shown to exert strong biological effects, and bergenin is effective for decreasing fibrosis in various organs.…”

“…Pathological staining of hepatocyte necrosis and Masson staining of collagen formation directly reflected the effectiveness of the drug, consistent with previous studies [ 13 ]. Furthermore, activation of HSCs, phenotypic changes, and ECM deposition are the central links in the occurrence of liver fibrosis [ 1 ]. Therefore, it is of great significance to study ECM components when evaluating the severity of liver fibrosis.…”

“…Liver fibrosis is a pathophysiological process in which various pathogenic factors continually damage the liver, resulting in extracellular matrix (ECM) deposition and fibrous scar formation [ 1 ]. According to statistics, more than one million people worldwide die of end-stage liver disease caused by liver fibrosis every year [ 2 ].…”

Targeting Small GTPases and Their Prenylation in Diabetes Mellitus

“…For selective targeting to the liver, several delivery methods, including the ones that use surface markers, were developed for liver cancer cells 296 and proposed for liver fibrosis. 297 In the case of muscle cells and adipocytes, selective targeting is challenging because of their high representation in the body. However, for skeletal muscle, surface recognition elements were identified and used for selective uptake.…”