Construction of hyaluronic acid-functionalized magnolol nanoparticles for ulcerative colitis treatment.

Oral targeted anti-inflammatory drugs have garnered significant interest in treating ulcerative colitis (UC) due to their potential in reducing medical costs and enhancing treatment efficacy. Magnolol (Mag), a natural anti-inflammatory compound, has demonstrated protective effects against UC. However, its application as an alternative therapeutic agent for UC is limited by poor gastrointestinal stability and inadequate accumulation at inflamed colonic lesions. This study introduces a novel nanoparticle (NPs) formulation based on Mag, functionalized with hyaluronic acid (HA) for targeted UC therapy. Bovine serum albumin (BSA) was modified with 2-thiamine hydrochloride to synthesize BSA·SH. Thiol-ene click reaction with Mag led to the formation of BSA·SH-Mag NPs, which were further modified with HA through dehydration condensation, regular spherical inflammation-targeting HA-BSA·SH-Mag nanoparticles with a charge of -23.6 mV and a particle size of 403 ± 4 nm were formed. In vitro studies revealed significant macrophage targeting and enhanced uptake by colon epithelial cells. Oral administration of HA-BSA·SH-Mag facilitated colon mucosal barrier repair by modulating pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), anti-inflammatory cytokines (IL-10), and tight junction proteins (ZO-1, Claudin, Occludin). Crucially, HA-BSA·SH-Mag was found to inhibit the JAK2/STAT3/NF-κB signaling pathway, reducing DSS-induced colon tissue inflammation. This research provides valuable insights into the oral use of natural compounds in UC therapy, highlighting the therapeutic potential of HA-BSA·SH-Mag NPs.