Targeting Hepatic Fibrosis

The application of targeted delivery systems has emerged as a rapidly evolving area of interest for the safe delivery of various drugs and nucleic acids for all kinds of diseases. Creative Biolabs is an undisputed global leader in drug delivery system discovery and provides development services targeting a wide variety of diseases. We offer high-quality targeted delivery services for hepatic fibrosis treatment. With combined expertise in protein chemistry, immunology, and molecular biology, our scientific team can help you with every step of the development process, from design to validation.

Hepatic Fibrosis

Liver fibrosis attributes to chronic damage to the liver in conjunction with the excessive accumulation of extracellular cell matrix (ECM) proteins, which is the main feature of most types of chronic liver diseases. The major causes of chronic liver diseases including alcohol abuse, hepatitis viral infections, genetic abnormalities, steatohepatitis, autoimmunity and other noninfectious diseases like fatty liver. The accumulation of ECM proteins contorts the hepatic architecture by forming a fibrous scar, and the subsequent development of nodules of regenerating hepatocytes defines cirrhosis or advanced liver fibrosis. Cirrhosis leads to hepatocellular dysfunction, hepatocellular carcinoma (HCC) and hepatic failure. Conventional therapy fails to treat liver diseases effectively due to the inability to deliver adequate concentration of therapeutic agents into the liver. Recently, nanotechnology serves as a novel treatment approach that has attracted more attention owing to the targeted delivery of therapeutic agents into the liver.

Fig.1 The mechanism of the pathological angiogenesis in hepatic fibrosis.¹

Delivery System Targeting Hepatic Fibrosis

A variety of nanoparticulate (NP) systems have been developed for the effective treatment of liver fibrosis by targeting hepatic stellate cell (HSC). The composition, architecture, shape, diverse size and surface properties of the NP systems determine their properties for the successful delivery of therapeutic precursor. Among various nanoparticulate delivery systems, inorganic NPs, liposomes and nanomicelles have been widely studied due to their unique properties to deliver drugs as well as other therapeutic moieties. In particular, liposomal NPs in clinical trials are considered to be a milestone in the treatment of hepatic fibrosis.

Fig.2 Different hepatic macrophage subsets function differently in distinct stages of liver fibrosis, and are modulated by various signaling pathways and regulatory molecules.²

Liposomes represent one of the potent carriers for delivering drugs to different pathological sites, and drug delivery through liposome-based drug nanocarriers is believed the most powerful tool for the treatment of liver fibrosis. The therapeutic potential of dexamethasone-loaded liposomes has been confirmed that the treatment significantly reduced both liver inflammation and liver fibrosis. These NPs are found to target hepatic macrophages by reducing T cells in the liver through an immune reaction, which results in the reduction of liver inflammation and fibrosis. Another study showed that cationic liposomes bearing microbubbles for the effective delivery of artificial microRNA, which was used to target connective tissue growth factor (CTGF) and can be useful for the inhibition of hepatic fibrosis. The ultrasound-mediated bubble destruction gene delivery of artificial microRNA in a dimethyl nitrosamine-induced fibrotic mouse model contributed to a decrease in fibrotic marker collagen, as well as a-SMA, by targeting CTGF.

What Can We Do for You?

Currently, treatment using a targeted delivery system such as NP systems is a promising tool for the therapy of vaious diseases including liver diseases. Creative Biolabs has focused on targeted delivery technology for years and we have built advanced module delivery systems. If you are interested in our services, please contact us for more details.

References

1. Li, Zhen, Junfeng Zhu, and Hao Ouyang. "Research progress of traditional Chinese medicine in improving hepatic fibrosis based on inhibiting pathological angiogenesis." Frontiers in Pharmacology 14 (2023): 1303012.
2. Gao, Chun-Chen, et al. "The versatility of macrophage heterogeneity in liver fibrosis." Frontiers in Immunology 13 (2022): 968879.

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