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1,087 results on '"Merlin, Didier"'

7. Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model.

Author

Mow, Rabeya Jafrin, Kuczma, Michal Pawel, Shi, Xiaodi, Mani, Sridhar, Merlin, Didier, and Yang, Chunhua

Subjects
INFLAMMATORY bowel diseases, DRUG delivery systems, ULCERATIVE colitis, EPITHELIAL cells, NANOPARTICLES
Abstract

A novel lipid nanoparticle (nLNP), formulated with three essential lipids to mimic ginger-derived exosomal particles, shows strong potential for delivering IL-22 mRNA specifically to the colon, presenting a unique oral drug delivery system for inflammatory bowel disease (IBD). However, its cellular targets and uptake behavior in healthy versus diseased colons remain unclear. Understanding these aspects is crucial for fully elucidating its targeting effectiveness in inflamed colon tissue. This study investigates the nLNP's cellular targets in healthy and diseased mouse colons. Flow cytometry compared nLNP uptake in healthy mice and a DSS-induced acute colitis model. The results revealed efficient internalization of nLNP by colonic epithelial cells in healthy and inflamed mice. In non-inflamed mice, the small number of colonic macrophages resulted in minimal uptake of nLNP by these cells. In inflamed mice, macrophages migrated to the damaged epithelium, where nLNP uptake was significantly increased, highlighting the nLNP's ability to target both epithelial and macrophage cells during inflammation. Additionally, safety assessments showed that the nLNP neither altered in vitro kinase activities nor exhibited immunotoxicity or induced in vivo toxicity at the maximum tolerated oral dose. These findings underscore the nLNP's safety and potential as a promising epithelial/macrophage-targeted drug delivery platform for oral ulcerative colitis (UC) treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Data from Early-Life Microbiota Exposure Restricts Myeloid-Derived Suppressor Cell–Driven Colonic Tumorigenesis

Author

Harusato, Akihito, primary, Viennois, Emilie, primary, Etienne-Mesmin, Lucie, primary, Matsuyama, Shingo, primary, Abo, Hirohito, primary, Osuka, Satoru, primary, Lukacs, Nicholas W., primary, Naito, Yuji, primary, Itoh, Yoshito, primary, Li, Jian-Dong, primary, Merlin, Didier, primary, Gewirtz, Andrew T., primary, and Denning, Timothy L., primary

Published
2023
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27. Supplementary Data File from Early-Life Microbiota Exposure Restricts Myeloid-Derived Suppressor Cell–Driven Colonic Tumorigenesis

Author

Harusato, Akihito, primary, Viennois, Emilie, primary, Etienne-Mesmin, Lucie, primary, Matsuyama, Shingo, primary, Abo, Hirohito, primary, Osuka, Satoru, primary, Lukacs, Nicholas W., primary, Naito, Yuji, primary, Itoh, Yoshito, primary, Li, Jian-Dong, primary, Merlin, Didier, primary, Gewirtz, Andrew T., primary, and Denning, Timothy L., primary

Published
2023
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31. Oral administration of M13-loaded nanoliposomes is safe and effective to treat colitis-associated cancer in mice

Author

Long, Dingpei, Alghoul, Zahra, Sung, Junsik, Yang, Chunhua, and Merlin, Didier

Abstract

Colitis-associated cancer (CAC) treatment lacks effective small-molecule drugs and efficient targeted delivery systems. Here, we loaded M13 (an anti-cancer drug candidate) to colon-targeting ginger-derived nanoliposomes (NL) and investigated if orally administered M13-NL could enhance the anticancer effects of M13 in CAC mouse models. The biopharmaceutical properties of M13 were assessed by physicochemical characterizations. The in vitro immunotoxicity of M13 was assessed against PBMCs using FACS and the mutagenic potential of M13 was evaluated by the Ames assay. The in vitro efficacy of M13 was tested in 2D- and 3D-cultured cancerous intestinal cells. AOM/DSS-induced CAC mice were used to evaluate the therapeutic effects of free M13 or M13-NL on CAC in vivo. M13 has beneficial physiochemical properties, including high stability, and no apparent immunotoxicity or mutagenic potential in vitro. M13 is effective against the growth of 2D- and 3D-cultured cancerous intestinal cells in vitro. The in vivo safety and efficacy of M13 were significantly improved by using NL for drug delivery (p < 0.001). Oral administration of M13-NL exhibited excellent therapeutic effects in AOM/DSS-induced CAC mice. M13-NL is a promising oral drug formulation for CAC treatment.

Published
2023
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