Mesoporous mixed oxides prepared by hard template methodology as novel drug delivery carriers for methotrexate

Non-silica-based metal oxide nanomaterials, especially those possessing significant porosity, are emerging as good candidates for the delivery of a range of chemotherapeutic drugs providing an enhanced biocompatibility in compares with silica-based nanocarriers. Herein, mesoporous materials were synthesized from hard-templated lanthanum-manganese (NC–LaMn) and barium-titanium (NC–BaTi) mixed oxides are evaluated as new drug nanocarriers, using methotrexate (MTX) as a model therapeutic compound. The SBA-15 material was used as a hard template to assist the sol-gel synthesis to provide the corresponding nanocarriers. The templated nanomaterials were characterized by X-ray diffraction (XRD), attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), dynamic light scattering (DLS), zeta potential analysis, transmission electron microscopy (TEM), N₂ adsorption-desorption isotherms, and thermogravimetric analysis (TGA), which revealed remarkably high surface area (S_BET ∼ 180 m²/g) and displayed mean nanoparticle sizes ∼ 700–1100 nm. The NC-LaMn and NC-BaTi carriers showed a loading efficiency of 47.2 mg/g and 70.1 mg/g for the encapsulation of MTX, respectively. Both mixed-metal oxides showed higher drug uptake than SBA-15 (22.6 mg/g) due to the higher alkalinity of the carriers, which promoted host-guest affinity by acid/base interactions. The carriers showed pH-dependent release of MTX and adjust their release profile at Korsmeyer-Peppas kinetics model. The release at pH = 5.5 for both mixed-oxides (k_NC-LaMn 0.077 and k_NC-BaTi 0.068) was faster than that at pH = 7.4 for (k_NC-LaMn 0.022 and k_NC-BaTi 0.019). Additionally, hemolysis and cell viability assays indicated that NC-BaTi was a biocompatible nanocarrier with no toxicity, whereas NC-LaMn was toxic even at low dosages for both red blood and HeLa cells. The results suggested that the synthesized NC-BaTi metal oxide had great potential as a nanocarrier in cancer therapy with optimal loading content and sustained release of MTX.