Oral colon-targeted responsive alginate/hyaluronic acid-based hydrogel propels the application of infliximab in colitis
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 m...
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| Published in: | International journal of biological macromolecules Vol. 249; p. 125952 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Elsevier B.V
30-09-2023
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| Abstract | 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. |
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| AbstractList | 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 Ca
/Zn
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. 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. |
| ArticleNumber | 125952 |
| Author | Pan, Jiaxing Zhu, Yun Du, Peng Duan, Yanming Xu, Huixiong Chen, Yingwen Ge, Wensong Pei, Mingliang Huai, Manxiu |
| Author_xml | – sequence: 1 givenname: Manxiu surname: Huai fullname: Huai, Manxiu organization: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, PR China – sequence: 2 givenname: Mingliang surname: Pei fullname: Pei, Mingliang email: peiml15@lzu.edu.cn organization: Central Laboratory, Department of Stomatology, Ultrasound Research and Education Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai 200072, PR China – sequence: 3 givenname: Jiaxing surname: Pan fullname: Pan, Jiaxing organization: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, PR China – sequence: 4 givenname: Yun surname: Zhu fullname: Zhu, Yun organization: Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, College of Stomatology, Shanghai Jiaotong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai 200011, PR China – sequence: 5 givenname: Yingwen surname: Chen fullname: Chen, Yingwen organization: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, PR China – sequence: 6 givenname: Peng surname: Du fullname: Du, Peng organization: Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, PR China – sequence: 7 givenname: Yanming surname: Duan fullname: Duan, Yanming organization: Department of Endoscopic Diagnosis and Treatment of Digestive Diseases, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, PR China – sequence: 8 givenname: Huixiong surname: Xu fullname: Xu, Huixiong email: xuhuixiong@126.com organization: Central Laboratory, Department of Stomatology, Ultrasound Research and Education Institute, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Yan-chang-zhong Road, Shanghai 200072, PR China – sequence: 9 givenname: Wensong surname: Ge fullname: Ge, Wensong email: gewensong@xinhuamed.com.cn organization: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, No. 1665 Kongjiang Road, Shanghai 200092, PR China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37494992$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_3390_molecules29061291 crossref_primary_10_1016_j_drudis_2024_104090 crossref_primary_10_1039_D3BM01645E crossref_primary_10_1016_j_ijbiomac_2024_133623 crossref_primary_10_1016_j_ijbiomac_2024_132178 |
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| Keywords | IBD Infliximab delivery Oral hydrogel |
| Language | English |
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