Design, synthesis and response surface optimization of a high-performance LaFeO3/Mg–Al layered double hydroxide/chitosan ternary nanocomposite as a pH-responsive carrier for controlled celecoxib release: experimental evaluation and kinetic modeling

Abstract

In this study, an advanced ternary nanocomposite, LaFeO₃/Mg–Al LDH/chitosan, was meticulously designed and synthesized as a pH-responsive controlled drug delivery system for the anti-inflammatory drug celecoxib. The LaFeO₃ precursor was synthesized via the sol–gel method and Mg–Al LDH was prepared through co-precipitation; the final nanocomposite was fabricated using ultrasonication and reflux techniques. Comprehensive characterization employing FT-IR, XRD, SEM, EDS, elemental mapping, and VSM confirmed the successful formation of a layered polymeric hybrid structure with uniform component distribution, ordered sheet-like morphology, and reduced magnetic properties compared to pristine LaFeO₃. Drug loading was investigated using the post-loading strategy, optimized via Response Surface Methodology (RSM) and Central Composite Design (CCD) by tuning key parameters: pH, temperature, and water : ethanol volumetric ratio. Under optimal conditions (pH = 9.38, temperature = 43.92 °C, water : ethanol ratio = 76.757), the drug loading efficiency (DLE) reached 98.72%, and the drug loading capacity (DLC) attained 43.96%, surpassing the performance of binary nanocomposites. The drug release profile exhibited pH-sensitivity, with faster release at pH 5.8 compared to pH 7.4. A biphasic release pattern was observed, characterized by an initial burst phase followed by sustained release, achieving approximately 90% release after 24 hours. The nanocomposite's swelling behavior was significantly higher under acidic conditions, indicating its pH-responsive behavior. Kinetic modeling revealed an anomalous transport mechanism (n = 0.62), controlled by combined molecular diffusion and matrix swelling. With its high loading capacity, controlled release, biocompatible main components, and environmental responsiveness, this nanocomposite emerges as a highly promising platform for pH-responsive controlled drug delivery systems.