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Rationally Designed Oral DOX Gels for Colon-Specific Administration

Colorectal cancer (CRC) is the third leading cause of death from cancer in both men and women. Traditional CRC dosage forms deliver the drug to both desired and unwanted sites of drug action, resulting in a number of negative side effects. Chemotherapeutic and chemopreventive agents are being target...

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Autores principales: Li, Jie, Ma, Luping, Wang, Cheng, Jiang, Pengju, Cui, Pengfei, Wang, Jianhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777853/
https://www.ncbi.nlm.nih.gov/pubmed/36547283
http://dx.doi.org/10.3390/gels8120759
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author Li, Jie
Ma, Luping
Wang, Cheng
Jiang, Pengju
Cui, Pengfei
Wang, Jianhao
author_facet Li, Jie
Ma, Luping
Wang, Cheng
Jiang, Pengju
Cui, Pengfei
Wang, Jianhao
author_sort Li, Jie
collection PubMed
description Colorectal cancer (CRC) is the third leading cause of death from cancer in both men and women. Traditional CRC dosage forms deliver the drug to both desired and unwanted sites of drug action, resulting in a number of negative side effects. Chemotherapeutic and chemopreventive agents are being targeted and delivered directly to the colon and rectum using targeted oral drug delivery systems. The main challenge in successfully targeting drugs to the colon via the oral route is avoiding drug absorption/degradation in the stomach and small intestine before the dosage form reaches the colon. In this study, we employed biocompatible chalk to adsorb DOX, then mixed pectin and cross-linked with calcium ions to form PC–DOX gels. The presence of cross-linked pectin and chalk can provide dual protection for the drug, significantly reducing drug leakage in gastric acid. In vitro release results showed that the designed PC–DOX could achieve 68% colon delivery efficiency. In the simulated colon environment, the released semi-degradable chalk did not affect the uptake of doxorubicin by colon cancer cells. Finally, in vivo simulation experiments in mice showed that rationally designed PC–DOX could achieve the highest colonic delivery efficiency. Our strategy has great potential for application in the treatment of colon cancer.
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spelling pubmed-97778532022-12-23 Rationally Designed Oral DOX Gels for Colon-Specific Administration Li, Jie Ma, Luping Wang, Cheng Jiang, Pengju Cui, Pengfei Wang, Jianhao Gels Article Colorectal cancer (CRC) is the third leading cause of death from cancer in both men and women. Traditional CRC dosage forms deliver the drug to both desired and unwanted sites of drug action, resulting in a number of negative side effects. Chemotherapeutic and chemopreventive agents are being targeted and delivered directly to the colon and rectum using targeted oral drug delivery systems. The main challenge in successfully targeting drugs to the colon via the oral route is avoiding drug absorption/degradation in the stomach and small intestine before the dosage form reaches the colon. In this study, we employed biocompatible chalk to adsorb DOX, then mixed pectin and cross-linked with calcium ions to form PC–DOX gels. The presence of cross-linked pectin and chalk can provide dual protection for the drug, significantly reducing drug leakage in gastric acid. In vitro release results showed that the designed PC–DOX could achieve 68% colon delivery efficiency. In the simulated colon environment, the released semi-degradable chalk did not affect the uptake of doxorubicin by colon cancer cells. Finally, in vivo simulation experiments in mice showed that rationally designed PC–DOX could achieve the highest colonic delivery efficiency. Our strategy has great potential for application in the treatment of colon cancer. MDPI 2022-11-22 /pmc/articles/PMC9777853/ /pubmed/36547283 http://dx.doi.org/10.3390/gels8120759 Text en © 2022 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
Li, Jie
Ma, Luping
Wang, Cheng
Jiang, Pengju
Cui, Pengfei
Wang, Jianhao
Rationally Designed Oral DOX Gels for Colon-Specific Administration
title Rationally Designed Oral DOX Gels for Colon-Specific Administration
title_full Rationally Designed Oral DOX Gels for Colon-Specific Administration
title_fullStr Rationally Designed Oral DOX Gels for Colon-Specific Administration
title_full_unstemmed Rationally Designed Oral DOX Gels for Colon-Specific Administration
title_short Rationally Designed Oral DOX Gels for Colon-Specific Administration
title_sort rationally designed oral dox gels for colon-specific administration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9777853/
https://www.ncbi.nlm.nih.gov/pubmed/36547283
http://dx.doi.org/10.3390/gels8120759
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