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Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity

Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulf...

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Autores principales: Andrgie, Abegaz Tizazu, Birhan, Yihenew Simegniew, Mekonnen, Tefera Worku, Hanurry, Endiries Yibru, Darge, Haile Fentahun, Lee, Rong-Ho, Chou, Hsiao-Ying, Tsai, Hsieh-Chih
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023610/
https://www.ncbi.nlm.nih.gov/pubmed/31892144
http://dx.doi.org/10.3390/polym12010043
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author Andrgie, Abegaz Tizazu
Birhan, Yihenew Simegniew
Mekonnen, Tefera Worku
Hanurry, Endiries Yibru
Darge, Haile Fentahun
Lee, Rong-Ho
Chou, Hsiao-Ying
Tsai, Hsieh-Chih
author_facet Andrgie, Abegaz Tizazu
Birhan, Yihenew Simegniew
Mekonnen, Tefera Worku
Hanurry, Endiries Yibru
Darge, Haile Fentahun
Lee, Rong-Ho
Chou, Hsiao-Ying
Tsai, Hsieh-Chih
author_sort Andrgie, Abegaz Tizazu
collection PubMed
description Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin–chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells.
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spelling pubmed-70236102020-03-11 Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity Andrgie, Abegaz Tizazu Birhan, Yihenew Simegniew Mekonnen, Tefera Worku Hanurry, Endiries Yibru Darge, Haile Fentahun Lee, Rong-Ho Chou, Hsiao-Ying Tsai, Hsieh-Chih Polymers (Basel) Article Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin–chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells. MDPI 2019-12-27 /pmc/articles/PMC7023610/ /pubmed/31892144 http://dx.doi.org/10.3390/polym12010043 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Andrgie, Abegaz Tizazu
Birhan, Yihenew Simegniew
Mekonnen, Tefera Worku
Hanurry, Endiries Yibru
Darge, Haile Fentahun
Lee, Rong-Ho
Chou, Hsiao-Ying
Tsai, Hsieh-Chih
Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity
title Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity
title_full Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity
title_fullStr Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity
title_full_unstemmed Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity
title_short Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity
title_sort redox-responsive heparin–chlorambucil conjugate polymeric prodrug for improved anti-tumor activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023610/
https://www.ncbi.nlm.nih.gov/pubmed/31892144
http://dx.doi.org/10.3390/polym12010043
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