Pickering emulsion as an oral delivery platform of anti-TNF-α antibody for ulcerative colitis therapy

Monoclonal antibodies that block pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) are effective therapy for inflammatory bowel diseases (IBD). However, intravenous infusion (IV), the standard route of administration of anti-TNF-α monoclonal antibodies (TNF-Ab), is time-consuming and inconvenient for patients. Recently, subcutaneously administered TNF-Ab formulations were developed for at-home injections of maintenance doses, but self-injection using needle-based pen systems can lead to low patient compliance. Therefore, an oral TNF-Ab formulation could significantly increase the medication adherence and quality of life of IBD patients. In this work, we developed a patient-friendly formulation based on a casein-stabilized Pickering emulsion for oral delivery of TNF-Ab (Casein-PE@TNF-Ab). Pickering emulsion was employed to protect TNF-Ab from gastric degradation and enhance colon residence time. Casein-PE@TNF-Ab exhibited a uniform particle size of 300 nm, a zeta potential of -45 mV, and encapsulation efficiency above 80%. In vitro studies showed enhanced uptake of Casein-PE@TNF-Ab by lipopolysaccharide-stimulated RAW264.7 macrophages compared with non-stimulated cells. In vivo imaging demonstrated prolonged colonic retention relative to free TNF-Ab. In DSS-induced colitis mice, oral Casein-PE@TNF-Ab markedly increased colon length and suppressed colonic TNF-α, IL-1β, and MPO levels by 82%, 61%, and 62%, respectively, versus DSS. Neutrophil infiltration in the colon also decreased by 46% relative to DSS group. The formulation remained stable for 3 months at 4 °C with preserved particle size and TNF-α-neutralizing activity. Together, these findings indicate that casein-stabilized Pickering emulsions provide a promising oral platform for antibody delivery and represent a viable strategy for ulcerative colitis therapy.