Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis
Abstract Ulcerative colitis is a chronic inflammatory bowel disease that strongly affects patient quality of life. Side effects of current therapies necessitate new treatment strategies that maximise the drug concentration at the site of inflammation, while minimizing systemic exposure. Capitalizing...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39013-3 |
| _version_ | 1797801357963427840 |
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| author | Marianna Carone Marianne R. Spalinger Robert A. Gaultney Raffaele Mezzenga Kristýna Hlavačková Aart Mookhoek Philippe Krebs Gerhard Rogler Paola Luciani Simone Aleandri |
| author_facet | Marianna Carone Marianne R. Spalinger Robert A. Gaultney Raffaele Mezzenga Kristýna Hlavačková Aart Mookhoek Philippe Krebs Gerhard Rogler Paola Luciani Simone Aleandri |
| author_sort | Marianna Carone |
| collection | DOAJ |
| description | Abstract Ulcerative colitis is a chronic inflammatory bowel disease that strongly affects patient quality of life. Side effects of current therapies necessitate new treatment strategies that maximise the drug concentration at the site of inflammation, while minimizing systemic exposure. Capitalizing on the biocompatible and biodegradable structure of lipid mesophases, we present a temperature-triggered in situ forming lipid gel for topical treatment of colitis. We show that the gel is versatile and can host and release drugs of different polarities, including tofacitinib and tacrolimus, in a sustained manner. Further, we demonstrate its adherence to the colonic wall for at least 6 h, thus preventing leakage and improving drug bioavailability. Importantly, we find that loading known colitis treatment drugs into the temperature-triggered gel improves animal health in two mouse models of acute colitis. Overall, our temperature-triggered gel may prove beneficial in ameliorating colitis and decreasing adverse effects associated with systemic application of immunosuppressive treatments. |
| first_indexed | 2024-03-13T04:49:14Z |
| format | Article |
| id | doaj.art-2d75cfd0314f4f04b7c907fb1bf398fb |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T04:49:14Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-2d75cfd0314f4f04b7c907fb1bf398fb2023-06-18T11:18:37ZengNature PortfolioNature Communications2041-17232023-06-0114111410.1038/s41467-023-39013-3Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitisMarianna Carone0Marianne R. Spalinger1Robert A. Gaultney2Raffaele Mezzenga3Kristýna Hlavačková4Aart Mookhoek5Philippe Krebs6Gerhard Rogler7Paola Luciani8Simone Aleandri9Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of BernDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of ZurichInstitute of Tissue Medicine and Pathology, University of BernLaboratory of Food & Soft Materials, Institute of Food, Nutrition and Health, IFNH; Department for Health Sciences and Technology, D-HEST, ETH ZurichInstitute of Tissue Medicine and Pathology, University of BernInstitute of Tissue Medicine and Pathology, University of BernInstitute of Tissue Medicine and Pathology, University of BernDepartment of Gastroenterology and Hepatology, University Hospital Zurich, University of ZurichDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of BernDepartment of Chemistry, Biochemistry and Pharmaceutical Sciences, University of BernAbstract Ulcerative colitis is a chronic inflammatory bowel disease that strongly affects patient quality of life. Side effects of current therapies necessitate new treatment strategies that maximise the drug concentration at the site of inflammation, while minimizing systemic exposure. Capitalizing on the biocompatible and biodegradable structure of lipid mesophases, we present a temperature-triggered in situ forming lipid gel for topical treatment of colitis. We show that the gel is versatile and can host and release drugs of different polarities, including tofacitinib and tacrolimus, in a sustained manner. Further, we demonstrate its adherence to the colonic wall for at least 6 h, thus preventing leakage and improving drug bioavailability. Importantly, we find that loading known colitis treatment drugs into the temperature-triggered gel improves animal health in two mouse models of acute colitis. Overall, our temperature-triggered gel may prove beneficial in ameliorating colitis and decreasing adverse effects associated with systemic application of immunosuppressive treatments.https://doi.org/10.1038/s41467-023-39013-3 |
| spellingShingle | Marianna Carone Marianne R. Spalinger Robert A. Gaultney Raffaele Mezzenga Kristýna Hlavačková Aart Mookhoek Philippe Krebs Gerhard Rogler Paola Luciani Simone Aleandri Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis Nature Communications |
| title | Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis |
| title_full | Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis |
| title_fullStr | Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis |
| title_full_unstemmed | Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis |
| title_short | Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis |
| title_sort | temperature triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis |
| url | https://doi.org/10.1038/s41467-023-39013-3 |
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