Advancing Biotherapeutic Treatment of Ulcerative Colitis Using Lipid Mesophases: Formulation Design and Preclinical Validation

Abstract

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 limit their widespread clinical use. Given the localized nature of UC, this study aimed to develop localized delivery strategies for infliximab (IFX), an anti‐tumor necrosis factor‐α (TNF‐α) monoclonal antibody recommended for moderately‐to‐severely active UC. Exploiting the intrinsic biocompatibility, mucoadhesion, and protein‐entrapment capacity of lipid mesophases (LMPs), IFX was encapsulated within the gel matrix, providing protection against enzymatic and environmental degradation. IFX‐LMPs were designed for targeted delivery to inflamed colonic tissues via rectal or oral administration, with oral dosage forms manufactured either by 3D printing or by encapsulation into enteric capsules. A comprehensive physicochemical characterization was performed to elucidate mesophase self‐assembly and its relationship with IFX release profiles in biorelevant fluids. The rectal gel demonstrated strong mucoadhesion, while LMP‐loaded enteric capsules enabled effective colon targeting. In a prophylactic treatment setting, LMP‐based formulations significantly attenuated disease progression and the development of severe inflammation compared with subcutaneous IFX. Overall, this study establishes a biocompatible delivery platform that enables colon‐targeted IFX release, representing a promising therapeutic strategy for UC using biotherapeutics.