Adsorption properties, the pH-sensitive release of 5-fluorouracil and cytotoxicity studies of mesoporous silica drug delivery matrix

Mesoporous silica materials were investigated as the carriers for pH-sensitive drug delivery systems. Porous silica SBA-15 was first functionalized by anchoring N[3-(trimethoxysilyl) propyl] aniline groups on the surface. After loading of an antineoplastic agent 5-fluorouracil, the pores were capped by beta-cyclodextrin molecules. The studied samples were characterized by N-2 adsorption/desorption measurements, thermal analysis, powder X-Ray Diffraction, and Transmission Electron Microscopy. Adsorption properties of 5-fluorouracil were explored via the construction of adsorption isotherms. The amount of 5-FU adsorbed on amine-functionalized SBA-15 was 60 mg per 1 g of solid. The adsorption of 5-fluorouracil on silica was also monitored by microcalorimetry, showing low adsorption enthalpies. Drug release properties from matrices were studied using UV-Visible spectroscopy with the un-blocked and blocked pores configuration to demonstrate the efficiency of the pH-responsive nanovalves and evaluated using different kinetic models. It was shown that no drug release occurred at neutral pH and that more than 80% of drug adsorbed amount was released at pH = 5. Working at the equilibrium, the initial burst of the drug from the silica surface, usually observed in other porous silica drug delivery systems, was avoided. The interaction between the beta-cyclodextrin molecules and grafted amine functions were also studied as a function of pH. Finally, the cytotoxicity tests were performed using human glioma U87 MG cells.