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<p>Metal-organic frameworks (MOFs), consisting of both organic linkers and metallic ions, are expected to be excellent drug delivery agents for the treatment of cancer. However, the stability of MOF in the gastrointestinal tract remains to be resolved. In this study, we synthesized a MOF, namely Zr-NDC. Next, a thiolated chitosan (TCS) surface-modified Zr-NDC was developed, providing a strong impetus for oral 5-FU delivery. The most favorable interaction sites between 5-FU and Zr-NDC were explored by computer simulation. Then, the physicochemical properties of TCS-MOF, such as particle size, size distribution, and morphology, were evaluated. Through a series of experiments, including in vitro drug release experiments, MTT analysis, and in situ single small intestinal perfusion (SPIP), the results showed that under the protection of TCS-MOF, the release rate (2.3%) of 5-FU in an acidic environment was far lower than in artificial intestinal juice (60%). The coating of TCS on the surface of Zr-NDC has the effect of controlling drug release. TCS coating can enhance the acid resistance limit of MOF and further increase the adhesion and permeability of 5-FU to the intestinal mucosa. It is expected that TCS-MOF@5-FU can serve as a potential drug delivery system for oral 5-FU.</p>

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Unveiling the Oral Therapeutic Promise of 5-Fluorouracil-Laden Thiol-Chitosan-Coated Metal-Organic Frameworks

  • 期刊论文

  • 发表日期：

    2025年4月28日

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  • Chen Yang,
  • Peng Cai

摘要

Metal-organic frameworks (MOFs), consisting of both organic linkers and metallic ions, are expected to be excellent drug delivery agents for the treatment of cancer. However, the stability of MOF in the gastrointestinal tract remains to be resolved. In this study, we synthesized a MOF, namely Zr-NDC. Next, a thiolated chitosan (TCS) surface-modified Zr-NDC was developed, providing a strong impetus for oral 5-FU delivery. The most favorable interaction sites between 5-FU and Zr-NDC were explored by computer simulation. Then, the physicochemical properties of TCS-MOF, such as particle size, size distribution, and morphology, were evaluated. Through a series of experiments, including in vitro drug release experiments, MTT analysis, and in situ single small intestinal perfusion (SPIP), the results showed that under the protection of TCS-MOF, the release rate (2.3%) of 5-FU in an acidic environment was far lower than in artificial intestinal juice (60%). The coating of TCS on the surface of Zr-NDC has the effect of controlling drug release. TCS coating can enhance the acid resistance limit of MOF and further increase the adhesion and permeability of 5-FU to the intestinal mucosa. It is expected that TCS-MOF@5-FU can serve as a potential drug delivery system for oral 5-FU.