Delivery of Ferulic Acid with PEGylated Diphenylalanine-Based Nanoparticles for the Treatment of Arthritis in Early Stage

Ferulic acid (FA), an active component extracted from Chinese medicine, shows excellent anti-inflammatory properties and favorable safety in various animal models. However, the application of FA as an anti-inflammatory drug is hindered by its instability and short half-life in vivo. In this paper, we synthesize PEGylated diphenylalanine nanoparticles by using glutaraldehyde (GTA) as a cross-linker of diphenylalanine NH2-Phe-Phe-COOH and poly(ethylene glycol) methyl ether amine (PEG(5k)-NH2). The PEGylated Phe-Phe nanoparticles are used to deliver FA for the treatment of Rheumatoid arthritis (RA). We find that the FA-loaded PEGylated Phe-Phe nanoparticles are biocompatible and inhibit the production of reactive oxygen species (ROS) from cells effectively. After being intravenously administrated in vivo, the FA-loaded PEGylated Phe-Phe nanoparticles show prolonged circulation time and accumulate in arthritic joints. More importantly, we show that the pre-arthritis treatment with the FA-loaded PEGylated Phe-Phe nanoparticles can significantly block the progression of RA.