Oral colon-targeted responsive alginate/hyaluronic acid-based hydrogel propels the application of infliximab in colitis

• Published in: International journal of biological macromolecules Vol. 249; p. 125952
• Main Authors: Huai, Manxiu, Pei, Mingliang, Pan, Jiaxing, Zhu, Yun, Chen, Yingwen, Du, Peng, Duan, Yanming, Xu, Huixiong, Ge, Wensong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30-09-2023
• Subjects: IBD; Infliximab delivery; Oral hydrogel; IBD; Infliximab delivery; Oral hydrogel
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2023.125952

Currently, commercialized infliximab (IFX) has rapidly propelled the clinical treatment of IBD, however, its inherent attributes, such as off-target effects and rapid metabolism, severely limit practical applications. Moreover, high doses injection of IFX can result in IBD treatment failure, which may induce other side effects. In this study, an colon microenvironment-responsive hydrogel (AL/HA hydrogel), consisting of acid-resistant sodium alginate and colon-degraded and targeted hyaluronic acid, was constructed by simple Ca2+/Zn2+ cross-linking. The ion-mediated hydrogel exhibited the protective effect of gastrointestinal tract to avoid early drug leakage, while the inflammation environments showed well-controlled drug release and significant biodegradable behaviors. Additionally, oral hydrogel exhibited long-standing enteritis areas compared with normal mice. Therefore, hydrogel-assisted enteritis treatment has great potential in IBD as an oral agent. After that, IFX was packaged in hydrogel to fabricate a facile oral antibody delivery system to treat IBD. IFX-embedded hydrogel showed remarkable therapeutic effect on IBD compared with free IFX. Surprisingly, oral hydrogel below 7 times IFX achieve the same amount of IFX-infused treatment that will further help alleviate the drawbacks of IFX. Our work elaborated on the efficacy of oral AL/HA@IFX in IBD, providing a guarantee for the future of promoted clinical transformation.
•A simple oral administration of hydrogel-mediated targeted enteritis was established.•Inflammatory region-excited hydrogel drive the use of commercialized infricimab in enteritis.•IFX-loaded hydrogel efficiently improve DSS-induced enteritis symptoms.•Basic design strategies facilitate future use of antibodies for clinical transformation.