The Polymer Society of Korea

Abstract

Fibrosis, caused by persistent tissue damage and chronic inflammation, leads to progressive organ dysfunction and contributes to heart failure and chronic lung diseases. Curcumin is a natural polyphenol which has shown promising antifibrotic activity, but its therapeutic application is hindered by its high hydrophobicity and potential cytotoxicity at high doses. Liquid–liquid phase separation (LLPS) is typically associated with high molecular weight biomolecules that form condensed phases to enable intracellular compartmentalization. Here, we demonstrate that LLPS can also be induced by low molecular weight drugs. In addition, we utilized the hydrophobicity of curcumin as the driving force for forming curcumin-rich coacervates. As a result, curcumin-based coacervates enhanced curcumin stability and achieved potent antifibrotic efficacy with minimal cytotoxicity, highlighting small-molecule LLPS as a promising and conceptually distinct strategy for antifibrotic therapy.