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<p>The number of colorectal cancer (CRC) cases is rising among younger people, making it the second most common cancer worldwide. A pH-responsive hydrogel containing chitosan-based microbeads (BHCMB) is proposed for the targeted oral delivery of bevacizumab as a potential treatment for CRC. The structural and functional properties of BHCMB formulations were validated through characterization via FTIR and XPS analyses. Investigations of in vitro drug release by hydrogels have demonstrated their responsiveness to pH variations, facilitating accurate dosing in physiological conditions. The HCT-116 colorectal cancer cell line was utilized to assess the in vitro anti-cancer properties of BHCMB hydrogel formulations. At 50&#xa0;µg/mL, BHCMB significantly reduced cell growth and caused apoptosis by damaging mitochondrial membranes and generating reactive oxygen species (ROS). The gene expression analysis revealed that BHCMB treatment significantly downregulated COX-2, IL-6, and BCL2 levels, while markedly upregulating p53 and Bax expression. Additionally, protein analysis in HCT-116 cells confirmed increased Bax and cleaved caspase-3 levels alongside reduced BCL2, indicating enhanced pro-apoptotic activity and potential anti-tumor effects in CRC. The in vivo study illustrates the efficacy of the BHCMB hydrogel in inhibiting CRC growth in a mice model. This research proposes an innovative pH-responsive hydrogel system for the oral administration of bevacizumab. The aim was to attain precise drug release at the colorectal tumor site, thereby enhancing apoptosis and effectively hindering CRC progression.</p> Graphical Abstract <p></p>

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Novel preparation of pH-responsive hydrogel with chitosan-based microbeads for targeted oral delivery of bevacizumab to enhanced apoptosis in azoxymethane-induced colorectal cancer: cellular and in vivo mice models

  • 期刊论文

  • 发表日期：

    2025年8月1日

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  • Tao You,
  • Jian Chen,
  • Yuesheng Zhu,
  • Na Shan,
  • Zejun Gao,
  • Yao Shen,
  • Yaojun Yu

摘要

The number of colorectal cancer (CRC) cases is rising among younger people, making it the second most common cancer worldwide. A pH-responsive hydrogel containing chitosan-based microbeads (BHCMB) is proposed for the targeted oral delivery of bevacizumab as a potential treatment for CRC. The structural and functional properties of BHCMB formulations were validated through characterization via FTIR and XPS analyses. Investigations of in vitro drug release by hydrogels have demonstrated their responsiveness to pH variations, facilitating accurate dosing in physiological conditions. The HCT-116 colorectal cancer cell line was utilized to assess the in vitro anti-cancer properties of BHCMB hydrogel formulations. At 50 µg/mL, BHCMB significantly reduced cell growth and caused apoptosis by damaging mitochondrial membranes and generating reactive oxygen species (ROS). The gene expression analysis revealed that BHCMB treatment significantly downregulated COX-2, IL-6, and BCL2 levels, while markedly upregulating p53 and Bax expression. Additionally, protein analysis in HCT-116 cells confirmed increased Bax and cleaved caspase-3 levels alongside reduced BCL2, indicating enhanced pro-apoptotic activity and potential anti-tumor effects in CRC. The in vivo study illustrates the efficacy of the BHCMB hydrogel in inhibiting CRC growth in a mice model. This research proposes an innovative pH-responsive hydrogel system for the oral administration of bevacizumab. The aim was to attain precise drug release at the colorectal tumor site, thereby enhancing apoptosis and effectively hindering CRC progression.

Graphical Abstract