Shifting Perspectives on Biotherapeutic Treatment in Ulcerative Colitis using Lipid Mesophases: Formulation Design and Preclinical Validation

Rafaela, G.; Tiziana, C.; Reto, C.; Emily, C.; Marlene, S.; Rogler, G.; Scharl, M.; Bergadano, A.; Mezzenga, R.; Kuentz, M.; Luciani, P.; Aleandri, S.

doi:10.64898/2026.02.09.701738

bioRxiv · 10.64898/2026.02.09.701738

Shifting Perspectives on Biotherapeutic Treatment in Ulcerative Colitis using Lipid Mesophases: Formulation Design and Preclinical Validation

Rafaela, G.·Tiziana, C.·Reto, C.·Emily, C.·Marlene, S.·Rogler, G.·Scharl, M.·Bergadano, A.·Mezzenga, R.·Kuentz, M.·Luciani, P.·Aleandri, S.

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Abstract

Biotherapeutics are required to achieve high remission rates in patients with severe ulcerative colitis (UC); however, adverse effects, complex dosing regimens, administration routes, and low patient compliance may limit their widespread clinical use. Given the localized nature of UC, this study aimed to develop and evaluate a localized delivery strategy for infliximab (IFX), an anti-tumor necrosis factor- (TNF-) monoclonal antibody (mAb) recommended by the European Crohns and Colitis Organization (ECCO) and the American Crohns & Colitis Foundation for moderately-to-severely active UC. Exploiting the intrinsic biocompatibility, mucoadhesivity, and protein-entrapment capacity of lipid mesophases (LMPs), IFX was encapsulated within the gel matrix, providing protection against enzymatic and environmental degradation. IFX-loaded LMPs were designed for targeted delivery to inflamed colonic tissues via rectal or oral administration, with patient-centric oral dosage forms manufactured using a 3D printing approach. A comprehensive physicochemical characterization was performed to elucidate mesophase self-assembly and its relationship with IFX release profiles in biorelevant fluids. Therapeutic efficacy was evaluated in vivo using a dextran sulfate sodium (DSS)-induced colitis rat model, which demonstrated rectal gel retention for at least 8 h and colonic targeting of the oral formulation within 6 h. Under severe inflammatory conditions, LMP-based formulations reduced disease activity, inflammatory biomarkers (TNF- and fecal lactoferrin), and colon shortening to values comparable to those of healthy controls, outperforming the therapeutic efficacy of subcutaneous IFX. Overall, this study establishes a biocompatible delivery platform that enables targeted colonic IFX release and suppresses systemic absorption, representing a promising advancement in the biotherapeutic treatment of UC.

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Rafaela, G., Tiziana, C., Reto, C., Emily, C., Marlene, S., Rogler, G., Scharl, M., Bergadano, A., Mezzenga, R., Kuentz, M., Luciani, P., Aleandri, S.. 2026-02-10. Shifting Perspectives on Biotherapeutic Treatment in Ulcerative Colitis using Lipid Mesophases: Formulation Design and Preclinical Validation. https://doi.org/10.64898/2026.02.09.701738

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