Thiol-Functionalized Mesoporous Silica Carriers for Clotrimazole: Synthesis, Textural Characterization, and Ph-Dependent Release Behaviour

Functionalized mesoporous silica particles were synthesized via a simplified sol–gel co-condensation method using mixed silica precursors—tetraethoxysilane (TEOS) and (3-mercaptopropyl) triethoxysilane (MPTES)—in two different molar ratios, alongside a reference non-functionalized MCM-41 sample. The obtained materials were characterized by nitrogen adsorption–desorption (BET–BJH–DFT) to assess their textural properties. The results confirmed a significant decrease in surface area and pore volume upon functionalization (from 1213 to 72.35 and 16.06 m² g⁻¹), accompanied by narrower pore diameters (2.4–3.5 nm), indicating partial pore blocking and increased surface tortuosity in the M1 and M2 samples. All materials demonstrated excellent carrier capacity for the hydrophobic antifungal drug clotrimazole (CLZ), achieving loading efficiencies close to 99% in all tested solvent media. The release behaviour was evaluated in acidic and mildly acidic environments (0.1 N HCl, KCl–HCl buffer pH 2, and acetate buffer pH 4.5). The best performance was observed when the same buffer was used for both drug loading and release, with cumulative release values between 51–91% at pH 2, while release remained in the 11–20% range at pH 4.5 and around 45% in 0.1 N HCl after 6 h. These findings highlight the influence of surface chemistry and pore architecture on drug–matrix interactions, confirming the potential of thiol-functionalized silica carriers for controlled delivery of hydrophobic drugs under pH-relevant conditions. The measured release time was evaluated for 24 hours via classical evaluation and for 3 hours and 20 minutes for the experiments performed with the dissolution instrument. The water: propan diol mixture solution has been chosen in order to mimic the pH of the skin level conditions. The different acidic solution has been chosen in order to mimic the acidic pH around a cancercell or around an inflammation. The extreme pH conditions (1 or 2) were chosen in order to model the dissolution of a drug with very low water solubility in an acidic environment. Moreover, these systems are very rarely studied in the literature.