Chitosan Nanoparticles as an Innovative Approach Against Liver Fibrosis

Liver fibrosis is a serious disease characterized by excessive deposition of connective tissue, which can progress to cirrhosis if left untreated. Conventional therapeutic approaches are often insufficient to halt the remodeling of liver tissue. In pharmaceutical research, nanotechnology-based drug delivery systems are therefore gaining increasing importance – particularly those based on chitosan nanoparticles.

Targeted Drug Delivery with Chitosan Nanoparticles

In a recent study, researchers developed a novel drug delivery system in which chitosan nanoparticles (CS-NPs) were modified with a specific peptide targeting the PDGFR-β receptor. This receptor plays a decisive role in the activation of hepatic stellate cells and thus in the development of fibrosis. These functionalized nanoparticles served as carriers for anti-TGF-β1 siRNA, small RNA molecules that specifically inhibit the expression of the pro-fibrotic factor TGF-β1. Additionally, collagenase was encapsulated into the chitosan particles to degrade already existing collagen deposits in the tissue.

Advantages of Chitosan as a Carrier Material

Chitosan is a natural polymer derived from chitin – for example, from crustacean shells. Due to its biocompatibility, biodegradability, and ability to form nanoparticles, it is ideally suited as a carrier material for sensitive therapeutics such as siRNA or enzymes. In this study, chitosan was crosslinked with sodium tripolyphosphate (TPP) in aqueous solution, resulting in stable nanoparticles. This technique allows for efficient encapsulation of active agents while ensuring controlled release. For future pharmaceutical applications, both highly purified medical-gradechitosan and specifically modified derivatives (e.g., cationically enhanced chitosan with defined degrees of deacetylation) could be used to further optimize loading efficiency and targeting precision.

Results and Outlook
In preclinical tests, the peptide-modified chitosan nanoparticles proved not only to be well tolerated but also to significantly reduce fibrosis markers in liver tissue. At the same time, the accumulation of nanoparticles in the damaged organ was markedly increased.
These results highlight the potential of chitosan-based nanoparticles as a promising platform for the treatment of chronic liver diseases. By combining targeted delivery with a dual-action approach (siRNA & enzyme), more effective therapies could be developed in the future – going beyond conventional drug treatments.

References
Mostafa S, Shetab Boushehri MA, Ezzat A, Weiskirchen R, Lamprecht A, Mansour S, Tammam SN. Targeted Delivery of Anti-TGF-β1 siRNA Using PDGFR-β Peptide-Modified Chitosan Nanoparticles for the Treatment of Liver Fibrosis. Molecular Pharmaceutics. 2025. doi:10.1021/acs.molpharmaceut.5c00715

First published on 9th of October 2025

Revised on 9th of October 2025