Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model
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...
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MDPI AG
2024-11-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/14/22/1800 |
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| author | Rabeya Jafrin Mow Michal Pawel Kuczma Xiaodi Shi Sridhar Mani Didier Merlin Chunhua Yang |
| author_facet | Rabeya Jafrin Mow Michal Pawel Kuczma Xiaodi Shi Sridhar Mani Didier Merlin Chunhua Yang |
| author_sort | Rabeya Jafrin Mow |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-71d732f067754c5ebb6197bfce2acb92 |
| institution | OA Journals |
| issn | 2079-4991 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj-art-71d732f067754c5ebb6197bfce2acb922025-08-20T01:54:08ZengMDPI AGNanomaterials2079-49912024-11-011422180010.3390/nano14221800Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse ModelRabeya Jafrin Mow0Michal Pawel Kuczma1Xiaodi Shi2Sridhar Mani3Didier Merlin4Chunhua Yang5Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USADigestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USADigestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USAAlbert Einstein College of Medicine, Bronx, NY 10461, USADigestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USADigestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USAA 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.https://www.mdpi.com/2079-4991/14/22/1800Inflammatory Bowel Disease (IBD)macrophage-targetinglipid labelingcolonic epitheliumflow cytometry |
| spellingShingle | Rabeya Jafrin Mow Michal Pawel Kuczma Xiaodi Shi Sridhar Mani Didier Merlin Chunhua Yang Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model Nanomaterials Inflammatory Bowel Disease (IBD) macrophage-targeting lipid labeling colonic epithelium flow cytometry |
| title | Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model |
| title_full | Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model |
| title_fullStr | Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model |
| title_full_unstemmed | Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model |
| title_short | Harnessing a Safe Novel Lipid Nanoparticle: Targeted Oral Delivery to Colonic Epithelial and Macrophage Cells in a Colitis Mouse Model |
| title_sort | harnessing a safe novel lipid nanoparticle targeted oral delivery to colonic epithelial and macrophage cells in a colitis mouse model |
| topic | Inflammatory Bowel Disease (IBD) macrophage-targeting lipid labeling colonic epithelium flow cytometry |
| url | https://www.mdpi.com/2079-4991/14/22/1800 |
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