Nanocomposites-based targeted oral drug delivery systems with infliximab in a murine colitis model.

Autor: Kim JM; Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea., Kim DH; Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea., Park HJ; Department of Integrated Bioscience and Biotechnology, Sejong University, 209 Neungdong‑ro, Gwangjin‑gu, Seoul, South Korea., Ma HW; Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea., Park IS; Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea., Son M; Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea., Ro SY; Department of Integrated Bioscience and Biotechnology, Sejong University, 209 Neungdong‑ro, Gwangjin‑gu, Seoul, South Korea., Hong S; Department of Integrated Bioscience and Biotechnology, Sejong University, 209 Neungdong‑ro, Gwangjin‑gu, Seoul, South Korea.; Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul, 05006, Republic of Korea., Han HK; College of Pharmacy, Dongguk University-Seoul, Dongguk‑ro‑32, Ilsan‑donggu, Goyang, South Korea., Lim SJ; Department of Integrated Bioscience and Biotechnology, Sejong University, 209 Neungdong‑ro, Gwangjin‑gu, Seoul, South Korea., Kim SW; Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. swk21c@hanmail.net.; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. swk21c@hanmail.net.; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. swk21c@hanmail.net., Cheon JH; Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea. GENIUSHEE@yuhs.ac.; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. GENIUSHEE@yuhs.ac.; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. GENIUSHEE@yuhs.ac.
Jazyk: angličtina
Zdroj: Journal of nanobiotechnology [J Nanobiotechnology] 2020 Sep 15; Vol. 18 (1), pp. 133. Date of Electronic Publication: 2020 Sep 15.
DOI: 10.1186/s12951-020-00693-4
Abstrakt: Background: Infliximab (IFX), a TNF-α blocking chimeric monoclonal antibody, induces clinical response and mucosal healing in patients with inflammatory bowel disease (IBD). However, systemic administration of this agent causes unwanted side effects. Oral delivery of antibody therapeutics might be an effective treatment strategy for IBD compared to intravenous administration.
Results: All three carriers had a high encapsulation efficiency, narrow size distribution, and minimal systemic exposure. There was a higher interaction between nanocomposite carriers and monocytes compared to lymphocytes in the PBMC of IBD patients. Orally administered nanocomposite carriers targeted to inflamed colitis minimized systemic exposure. All IFX delivery formulations with nanocomposite carriers had a significantly less colitis-induced body weight loss, colon shortening and histomorphological score, compared to the DSS-treated group. AC-IFX-L and EAC-IFX-L groups showed significantly higher improvement of the disease activity index, compared to the DSS-treated group. In addition, AC-IFX-L and EAC-IFX-L alleviated pro-inflammatory cytokine expressions (Tnfa, Il1b, and Il17).
Conclusion: We present orally administered antibody delivery systems which improved efficacy in murine colitis while reducing systemic exposure. These oral delivery systems suggest a promising therapeutic approach for treating IBD.
Databáze: MEDLINE
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