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Evaluation of the Effect of an Intraperitoneal Cytostatic-Loaded Supramolecular Hydrogel on Intestinal Anastomotic Healing in an Animal Model
The prognosis of colorectal cancer patients with peritoneal metastases is very poor. Intraperitoneal drug delivery systems, like supramolecular hydrogels, are being developed to improve local delivery and intraperitoneal residence time of a cytostatic such as mitomycin C (MMC). In this study, we eva...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10608244/ https://www.ncbi.nlm.nih.gov/pubmed/37895458 http://dx.doi.org/10.3390/life13102076 |
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author | Heuvelings, Danique J. I. Wintjens, Anne G. W. E. Jongen, Audrey C. H. M. Gielen, Maurits J. C. A. M. Lenaerts, Kaatje Fransen, Peter-Paul K. H. Gijbels, Marion J. van Almen, Geert C. Dankers, Patricia Y. W. de Hingh, Ignace H. J. T. Bouvy, Nicole D. |
author_facet | Heuvelings, Danique J. I. Wintjens, Anne G. W. E. Jongen, Audrey C. H. M. Gielen, Maurits J. C. A. M. Lenaerts, Kaatje Fransen, Peter-Paul K. H. Gijbels, Marion J. van Almen, Geert C. Dankers, Patricia Y. W. de Hingh, Ignace H. J. T. Bouvy, Nicole D. |
author_sort | Heuvelings, Danique J. I. |
collection | PubMed |
description | The prognosis of colorectal cancer patients with peritoneal metastases is very poor. Intraperitoneal drug delivery systems, like supramolecular hydrogels, are being developed to improve local delivery and intraperitoneal residence time of a cytostatic such as mitomycin C (MMC). In this study, we evaluate the effect of intraperitoneal hydrogel administration on anastomotic healing. Forty-two healthy Wistar rats received a colonic end-to-end anastomosis, after which 6 animals received an intraperitoneal injection with saline, 18 with unloaded hydrogel and 18 with MMC-loaded hydrogel. After 7 days, animals were euthanized, and the anastomotic adhesion and leakage score were measured as primary outcome. Secondary outcomes were bursting pressure, histological anastomosis evaluation and body weight changes. Twenty-two rats completed the follow-up period (saline: n = 6, unloaded hydrogel: n = 10, MMC-loaded hydrogel: n = 6) and were included in the analysis. A trend towards significance was found for anastomotic leakage score between the rats receiving saline and unloaded hydrogel after multiple-comparison correction (p = 0.020, α = 0.0167). No significant differences were found for all other outcomes. The main reason for drop-out in this study was intestinal blood loss. Although the preliminary results suggest that MMC-loaded or unloaded hydrogel does not influence anastomotic healing, the intestinal blood loss observed in a considerable number of animals receiving unloaded and MMC-loaded hydrogel implies that the injection of the hydrogel under the studied conditions is not safe in the current rodent model and warrants further optimalisation of the hydrogel. |
format | Online Article Text |
id | pubmed-10608244 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106082442023-10-28 Evaluation of the Effect of an Intraperitoneal Cytostatic-Loaded Supramolecular Hydrogel on Intestinal Anastomotic Healing in an Animal Model Heuvelings, Danique J. I. Wintjens, Anne G. W. E. Jongen, Audrey C. H. M. Gielen, Maurits J. C. A. M. Lenaerts, Kaatje Fransen, Peter-Paul K. H. Gijbels, Marion J. van Almen, Geert C. Dankers, Patricia Y. W. de Hingh, Ignace H. J. T. Bouvy, Nicole D. Life (Basel) Article The prognosis of colorectal cancer patients with peritoneal metastases is very poor. Intraperitoneal drug delivery systems, like supramolecular hydrogels, are being developed to improve local delivery and intraperitoneal residence time of a cytostatic such as mitomycin C (MMC). In this study, we evaluate the effect of intraperitoneal hydrogel administration on anastomotic healing. Forty-two healthy Wistar rats received a colonic end-to-end anastomosis, after which 6 animals received an intraperitoneal injection with saline, 18 with unloaded hydrogel and 18 with MMC-loaded hydrogel. After 7 days, animals were euthanized, and the anastomotic adhesion and leakage score were measured as primary outcome. Secondary outcomes were bursting pressure, histological anastomosis evaluation and body weight changes. Twenty-two rats completed the follow-up period (saline: n = 6, unloaded hydrogel: n = 10, MMC-loaded hydrogel: n = 6) and were included in the analysis. A trend towards significance was found for anastomotic leakage score between the rats receiving saline and unloaded hydrogel after multiple-comparison correction (p = 0.020, α = 0.0167). No significant differences were found for all other outcomes. The main reason for drop-out in this study was intestinal blood loss. Although the preliminary results suggest that MMC-loaded or unloaded hydrogel does not influence anastomotic healing, the intestinal blood loss observed in a considerable number of animals receiving unloaded and MMC-loaded hydrogel implies that the injection of the hydrogel under the studied conditions is not safe in the current rodent model and warrants further optimalisation of the hydrogel. MDPI 2023-10-18 /pmc/articles/PMC10608244/ /pubmed/37895458 http://dx.doi.org/10.3390/life13102076 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Heuvelings, Danique J. I. Wintjens, Anne G. W. E. Jongen, Audrey C. H. M. Gielen, Maurits J. C. A. M. Lenaerts, Kaatje Fransen, Peter-Paul K. H. Gijbels, Marion J. van Almen, Geert C. Dankers, Patricia Y. W. de Hingh, Ignace H. J. T. Bouvy, Nicole D. Evaluation of the Effect of an Intraperitoneal Cytostatic-Loaded Supramolecular Hydrogel on Intestinal Anastomotic Healing in an Animal Model |
title | Evaluation of the Effect of an Intraperitoneal Cytostatic-Loaded Supramolecular Hydrogel on Intestinal Anastomotic Healing in an Animal Model |
title_full | Evaluation of the Effect of an Intraperitoneal Cytostatic-Loaded Supramolecular Hydrogel on Intestinal Anastomotic Healing in an Animal Model |
title_fullStr | Evaluation of the Effect of an Intraperitoneal Cytostatic-Loaded Supramolecular Hydrogel on Intestinal Anastomotic Healing in an Animal Model |
title_full_unstemmed | Evaluation of the Effect of an Intraperitoneal Cytostatic-Loaded Supramolecular Hydrogel on Intestinal Anastomotic Healing in an Animal Model |
title_short | Evaluation of the Effect of an Intraperitoneal Cytostatic-Loaded Supramolecular Hydrogel on Intestinal Anastomotic Healing in an Animal Model |
title_sort | evaluation of the effect of an intraperitoneal cytostatic-loaded supramolecular hydrogel on intestinal anastomotic healing in an animal model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10608244/ https://www.ncbi.nlm.nih.gov/pubmed/37895458 http://dx.doi.org/10.3390/life13102076 |
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