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<p>The development of smart drug delivery systems (DDS) is essential for enhancing therapeutic efficacy while minimising adverse effects. In this work, a biocompatible carboxymethylcellulose/metal–organic framework composite (CMC/MIL-88B(Fe)) was synthesised via an ultrasound-assisted method to achieve controlled and pH-responsive delivery of dexamethasone (DEX). Structural analyses (FT-IR, XRD, FE-SEM/EDX, TGA/DSC, BET) confirmed the successful incorporation of MIL-88B(Fe) nanostructures within the CMC matrix, generating a mesoporous architecture suitable for drug loading. DEX loading efficiencies were 82.7% for CMC/MIL-88B(Fe) and 88.6% for pristine MIL-88B(Fe), consistent with molecular docking results showing a slightly stronger interaction with MIL-88B(Fe). In vitro release profiles revealed a pronounced pH-dependent behaviour: after 240&#xa0;h, CMC/MIL-88B(Fe)/DEX released 39.8% (pH 7.4) and 78.2% (pH 5), while MIL-88B(Fe)/DEX released 59.4% and 83.9%, respectively. The CMC/MIL-88B(Fe) composite exhibited reduced burst release during the first 24&#xa0;h (25.3% at pH 7.4; 39.8% at pH 5) compared to MIL-88B(Fe) (42.6% at pH 7.4; and 58.4% at pH 5), confirming the diffusion-retarding effect of the CMC coating. Kinetic modelling showed strong agreement with the Weibull model (R<sup>2</sup> &gt; 0.99), indicating diffusion-controlled release. Cytotoxicity assays on A549 cell line demonstrated good biocompatibility of CMC/MIL-88B(Fe), with &gt; 60% viability at 4&#xa0;mg/mL, while the CMC/MIL-88B(Fe)/DEX showed reduced toxicity due to sustained release. The CMC/MIL-88B(Fe)/DEX also exhibited enhanced enzymatic biodegradability (76% in 10 days) and improved colloidal stability. Therefore, CMC/MIL-88B(Fe)/DEX represents a promising platform for controlled, pH-responsive delivery of DEX in acidic inflammatory microenvironments.</p> Graphical Abstract <p></p>

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Synthesis and Characterization of a pH-Responsive CMC/MIL-88B(Fe) Bio-Nanocomposite for Controlled Dexamethasone Delivery

  • 期刊论文

  • 发表日期：

    2025年12月18日

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  • Mohammad Reza Darparesh,
  • Ramin Karimian,
  • Mahdi Fasihi-Ramandi,
  • Mohammad Reza Khodabakhshi

摘要

The development of smart drug delivery systems (DDS) is essential for enhancing therapeutic efficacy while minimising adverse effects. In this work, a biocompatible carboxymethylcellulose/metal–organic framework composite (CMC/MIL-88B(Fe)) was synthesised via an ultrasound-assisted method to achieve controlled and pH-responsive delivery of dexamethasone (DEX). Structural analyses (FT-IR, XRD, FE-SEM/EDX, TGA/DSC, BET) confirmed the successful incorporation of MIL-88B(Fe) nanostructures within the CMC matrix, generating a mesoporous architecture suitable for drug loading. DEX loading efficiencies were 82.7% for CMC/MIL-88B(Fe) and 88.6% for pristine MIL-88B(Fe), consistent with molecular docking results showing a slightly stronger interaction with MIL-88B(Fe). In vitro release profiles revealed a pronounced pH-dependent behaviour: after 240 h, CMC/MIL-88B(Fe)/DEX released 39.8% (pH 7.4) and 78.2% (pH 5), while MIL-88B(Fe)/DEX released 59.4% and 83.9%, respectively. The CMC/MIL-88B(Fe) composite exhibited reduced burst release during the first 24 h (25.3% at pH 7.4; 39.8% at pH 5) compared to MIL-88B(Fe) (42.6% at pH 7.4; and 58.4% at pH 5), confirming the diffusion-retarding effect of the CMC coating. Kinetic modelling showed strong agreement with the Weibull model (R2 > 0.99), indicating diffusion-controlled release. Cytotoxicity assays on A549 cell line demonstrated good biocompatibility of CMC/MIL-88B(Fe), with > 60% viability at 4 mg/mL, while the CMC/MIL-88B(Fe)/DEX showed reduced toxicity due to sustained release. The CMC/MIL-88B(Fe)/DEX also exhibited enhanced enzymatic biodegradability (76% in 10 days) and improved colloidal stability. Therefore, CMC/MIL-88B(Fe)/DEX represents a promising platform for controlled, pH-responsive delivery of DEX in acidic inflammatory microenvironments.

Graphical Abstract