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Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors

The efficacy of treating solid tumors with chemotherapy is primarily hindered by dose-limiting toxicity due to off-target effects and the heterogeneous drug distribution caused by the dense extracellular matrix. The enhanced permeability and retention (EPR) effect within tumors restricts the circula...

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Autores principales: Li, Na, Lin, Jianjun, Liu, Chunping, Zhang, Qian, Li, Riwang, Wang, Chuang, Zhao, Chaochao, Lu, Lu, Zhou, Changren, Tian, Jinhuan, Ding, Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669971/
https://www.ncbi.nlm.nih.gov/pubmed/36406213
http://dx.doi.org/10.3389/fbioe.2022.1043939
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author Li, Na
Lin, Jianjun
Liu, Chunping
Zhang, Qian
Li, Riwang
Wang, Chuang
Zhao, Chaochao
Lu, Lu
Zhou, Changren
Tian, Jinhuan
Ding, Shan
author_facet Li, Na
Lin, Jianjun
Liu, Chunping
Zhang, Qian
Li, Riwang
Wang, Chuang
Zhao, Chaochao
Lu, Lu
Zhou, Changren
Tian, Jinhuan
Ding, Shan
author_sort Li, Na
collection PubMed
description The efficacy of treating solid tumors with chemotherapy is primarily hindered by dose-limiting toxicity due to off-target effects and the heterogeneous drug distribution caused by the dense extracellular matrix. The enhanced permeability and retention (EPR) effect within tumors restricts the circulation and diffusion of drugs. To overcome these obstacles, hydrogels formed in situ at the tumor site have been proposed to promote drug accumulation, retention, and long-lasting release. We developed a thiolated chitosan (CSSH) hydrogel with a gelation point of 37°C. Due to the pH-sensitive characteristics of disulfides, the prepared hydrogel facilitated drug release in the acidic tumor environment. A drug release system composed of hydrophilic doxorubicin (Dox) and hydrophobic liposome-encapsulated curcumin (Cur–Lip) was designed to enhance the long-lasting therapeutic impacts and reduce adverse side effects. These composite gels possess a suitable gelation time of approximately 8–12 min under physiological conditions. The cumulative release ratio was higher at pH = 5.5 than at pH = 7.4 over the first 24 h, during which approximately 10% of the Dox was released, and Cur was released slowly over the following 24–120 h. Cell assays indicated that the Cur–Lip/Dox/CSSH gels effectively inhibited the growth of cancer cells. These in situ-formed Cur–Lip/Dox gels with long-term drug release capabilities have potential applications for tumor suppression and tissue regeneration after surgical tumor resection.
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spelling pubmed-96699712022-11-18 Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors Li, Na Lin, Jianjun Liu, Chunping Zhang, Qian Li, Riwang Wang, Chuang Zhao, Chaochao Lu, Lu Zhou, Changren Tian, Jinhuan Ding, Shan Front Bioeng Biotechnol Bioengineering and Biotechnology The efficacy of treating solid tumors with chemotherapy is primarily hindered by dose-limiting toxicity due to off-target effects and the heterogeneous drug distribution caused by the dense extracellular matrix. The enhanced permeability and retention (EPR) effect within tumors restricts the circulation and diffusion of drugs. To overcome these obstacles, hydrogels formed in situ at the tumor site have been proposed to promote drug accumulation, retention, and long-lasting release. We developed a thiolated chitosan (CSSH) hydrogel with a gelation point of 37°C. Due to the pH-sensitive characteristics of disulfides, the prepared hydrogel facilitated drug release in the acidic tumor environment. A drug release system composed of hydrophilic doxorubicin (Dox) and hydrophobic liposome-encapsulated curcumin (Cur–Lip) was designed to enhance the long-lasting therapeutic impacts and reduce adverse side effects. These composite gels possess a suitable gelation time of approximately 8–12 min under physiological conditions. The cumulative release ratio was higher at pH = 5.5 than at pH = 7.4 over the first 24 h, during which approximately 10% of the Dox was released, and Cur was released slowly over the following 24–120 h. Cell assays indicated that the Cur–Lip/Dox/CSSH gels effectively inhibited the growth of cancer cells. These in situ-formed Cur–Lip/Dox gels with long-term drug release capabilities have potential applications for tumor suppression and tissue regeneration after surgical tumor resection. Frontiers Media S.A. 2022-11-03 /pmc/articles/PMC9669971/ /pubmed/36406213 http://dx.doi.org/10.3389/fbioe.2022.1043939 Text en Copyright © 2022 Li, Lin, Liu, Zhang, Li, Wang, Zhao, Lu, Zhou, Tian and Ding. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Li, Na
Lin, Jianjun
Liu, Chunping
Zhang, Qian
Li, Riwang
Wang, Chuang
Zhao, Chaochao
Lu, Lu
Zhou, Changren
Tian, Jinhuan
Ding, Shan
Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors
title Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors
title_full Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors
title_fullStr Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors
title_full_unstemmed Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors
title_short Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors
title_sort temperature- and ph-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669971/
https://www.ncbi.nlm.nih.gov/pubmed/36406213
http://dx.doi.org/10.3389/fbioe.2022.1043939
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