Controlled release of isoniazid by hybrid systems

Abstract

Clays and polysaccharides have emerged as promising platforms for drug delivery due to their biocompatibility, tunable properties, and cost-effectiveness. This study investigates the potential of smectite clays and modified pullulan hydrogels as drug carriers for isoniazid (INH), a first-line treatment for tuberculosis. Seven natural and synthetic clays were characterized by XRF, XRD, FTIR, BET, and TGA to explore the relationship between pore volume, surface charge, and INH adsorption/release. The clay exhibiting an ideal pore volume (~0.100 cm³/g) displayed superior retention and sustained release in neural environment. Optimal adsorption (~115 mg/g) was achieved with montmorillonite at pH 2, where INH is positively charged and interacts more strongly with negatively charged clay surfaces. Comparative tests with Laponite, a hectorite clay type, revealed that surface charge and pore structure significantly influence both incorporation and release efficiency, with montmorillonite releasing less than 8% INH under simulated gastric conditions. Adsorption mechanisms varied with pH, transitioning from monolayer to multilayer regimes, which in turn influenced the release kinetics. Monolayer-loaded hybrids followed a zero-order release profile (R² > 0.93), offering steady and controlled delivery. Cytocompatibility tests confirmed the safety of the clay-based systems. In parallel, pullulan was functionalized with methacrylic anhydride to enable UV cross-linking, forming hydrogels with tunable swelling properties. The degree of functionalization was confirmed by H-NMR and FTIR. Crosslinking degree, confirmed by rheology, directly impacted the hydrogel swelling capacity and INH release profiles under gastrointestinal conditions (pH 7.4). The pullulan hydrogels demonstrated green-processing advantages and potential for sustained drug delivery. Together, these findings provide valuable insights into the design of advanced, pH-responsive drug delivery systems. By elucidating the interplay between material structure, drug state, and release behavior, this work supports the development of optimized carriers for tuberculosis therapy and highlights the complementary potential of natural clays and modified biopolymers in biomedical applications.

Date	15 Aug 2025
Original language	American English
Awarding Institution	École de technologie supérieure
Supervisor	Nicole R. Demarquette (Supervisor) & Francisco Rolando Valenzuela-Diaz (Co-supervisor)