Synthesis and characterisation of a pH-responsive carboxymethylcellulose/metal-organic framework CMC/MIL-88B(Fe) bio-nanocomposite for controlled dexamethasone delivery

The development of smart drug delivery systems (DDS) has become essential for improving therapeutic efficiency while minimising adverse effects. In this work, a biocompatible carboxymethylcellulose / metal-organic framework composite (CMC/MIL-88B(Fe)) was designed and synthesised through an ultrasound-assisted method to achieve controlled and pH-responsive delivery of dexamethasone (DEX). The obtained material was thoroughly characterised using FT-IR, XRD, TGA/DSC, N₂ adsorption–desorption, and FE-SEM/EDX analyses, confirming the successful formation of MIL-88B(Fe) crystals uniformly distributed within the amorphous CMC network. The composite exhibited a mesoporous structure and good drug-loading performance, achieving an encapsulation efficiency of about 82.7%. In vitro release studies revealed distinct pH-dependent release behaviour, where nearly 78% of DEX was released at acidic pH 5.0 in 240 h compared to 39% at physiological pH 7.4. Drug release kinetics followed the Weibull model (R² >0.96), indicating diffusion-controlled release. To evaluate the biocompatibility and cytotoxic potential, an MTT assay was performed using A549 human lung adenocarcinoma cells. Cells were treated with increasing concentrations (0.05–4 mg/mL) of CMC/MIL-88B(Fe), DEX, and CMC/MIL-88B(Fe)/DEX for 48 h. The CMC/MIL-88B(Fe) maintained over 60% cell viability even at the highest concentration, confirming good biocompatibility and negligible intrinsic cytotoxicity. In contrast, free DEX reduced cell viability to about 45% at 4 mg/mL, while the CMC/MIL-88B(Fe)/DEX system exhibited lower cytotoxicity at the same dose, due to the controlled and sustained drug release from the hybrid matrix. These findings highlight the excellent cytocompatibility and controlled delivery performance of CMC/MIL-88B(Fe), making it a promising platform for safe and efficient corticosteroid delivery in inflammatory and tumour-related applications.