Callicarpa nudiflora-derived extracellular vesicle-like particles loaded with budesonide enhance the treatment of ulcerative colitis by regulating M1/M2 macrophage polarization.

Conventional drug therapy effectively controls early-stage ulcerative colitis (UC) symptoms, but long-term use and high doses may compromise safety and patient tolerance. Here, Callicarpa nudiflora-derived extracellular vesicle-like particle (CN-EVLP) was extracted from the fresh leaves of Callicarpa nudiflora. An oral delivery system of budesonide using CN-EVLP (CN-EVLP-Bud) was designed, and the loading conditions were explored and optimized to improve the encapsulation efficiency and drug loading. We found that encapsulating budesonide in CN-EVLP enhanced its biocompatibility and promoted cellular uptake in both Caco-2 and Raw264.7 cells. In lipopolysaccharide-induced RAW264.7 cells and dextran sulfate sodium (DSS)-induced murine colitis models, CN-EVLP-Bud showed significantly stronger anti-inflammatory and antioxidant effects than free budesonide, including suppressing pro-inflammatory cytokines (IL-6, TNF-α) and reducing oxidative stress. Moreover, CN-EVLP could modulate macrophage M1/M2 polarization, further enhancing its anti-inflammatory efficacy. Thus, CN-EVLP shows promising potential as a novel nanomedicine delivery vehicle for UC therapy.