What question did this study set out to answer?

To evaluate the effectiveness of a multifunctional oral nanoplatform for delivering upadacitinib in ulcerative colitis treatment.

April 27, 2026Open Access

Layer-by-layer engineered outer membrane vesicles enable oral upadacitinib delivery for inflammation control and fibrosis attenuation in ulcerative colitis

Key Points

To evaluate the effectiveness of a multifunctional oral nanoplatform for delivering upadacitinib in ulcerative colitis treatment.
Developed a layer-by-layer coated outer membrane vesicle (OMV-LbL@Upa) nanoplatform, encapsulating upadacitinib.
Assessed the oral delivery system's stability and intestinal retention in acute and chronic UC models.
Evaluated changes in disease activity and intestinal health markers post-treatment.
OML-LbL@Upa significantly improved disease activity in UC models, with a notable reduction in inflammation.
Restored tight junction proteins and corrected intestinal permeability, improving overall gut function.
Inhibited JAK-STAT signaling pathways, leading to decreased collagen deposition and lower levels of pro-fibrotic markers.

Abstract

Ulcerative colitis (UC) is characterized by intertwined defects in the epithelial barrier, microbiota composition, and immune signaling, which collectively sustain inflammation and drive fibrosis. Here, we report a multifunctional oral nanoplatform OMV-LbL@Upa (OUL), comprising probiotic-derived outer membrane vesicles (OMVs) encapsulating the JAK-STAT inhibitor upadacitinib (Upa), further functionalized with a trans-cinnamic acid/chitosan-based layer-by-layer (LbL) coating. The LbL architecture significantly enhanced gastric stability and intestinal retention, enabling colon-targeted release while preserving OMV bioactivity. In both acute and chronic UC models, OUL significantly improved disease activity, restored tight junction proteins, corrected intestinal permeability, rebalanced gut microbiota, and reprogrammed macrophage polarization. Mechanistically, OUL suppressed JAK-STAT signaling pathways, culminating in attenuated collagen deposition and the downregulation of pro-fibrotic markers (α-SMA and vimentin). With no overt systemic toxicity observed, this orally administered nanoplatform integrates microbiota/epithelial restoration with targeted JAK1 inhibition to achieve anti-inflammatory and anti-fibrotic benefits, offering a clinically promising strategy for the management of UC.

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