Cytotoxicity study and influence of SBA-15 surface polarity and pH on adsorption and release properties of anticancer agent pemetrexed.

Mesoporous material SBA-15 was functionalized with different polar and nonpolar groups: 3-aminopropyl, (SBA-15-NH2), 3-isocyanatopropyl (SBA-15-NCO), 3-mercaptopropyl (SBA-15-SH), methyl (SBA-15-CH3) and phenyl (SBA-15-Ph). The resulting surface grafted materials were investigated as matrices for controlled drug delivery. Anticancer agent, pemetrexed (disodium pemetrexed heptahydrate) was selected as a model drug and loaded in the unmodified and functionalized SBA-15 materials. Materials were characterized by elemental analysis, infrared spectroscopy, transmission electron microscopy, nitrogen adsorption/desorption analysis, small angle X-ray scattering, powder X-ray diffraction, solid state NMR spectroscopy and thermogravimetry. It was shown that surface modification has an impact on both encapsulated drug amount and release properties. Release experiments were performed into two media with different pH: simulated body fluid (pH = 7.4) and simulated gastric fluid (pH = 2). In general, the effect of pH was reflected by the lower release of pemetrexed under acidic conditions (pH = 2) compared to slightly alkaline saline environment (pH = 7.4). The release rate of pemetrexed from propylamine-, propylisocyanate- and phenyl-modified SBA-15 was found to be effectively controlled by intermolecular interactions as compared to that from pure SBA-15, SBA-15-SH, and SBA-15-CH3, that evidenced a steady and similar release. The highest release was observed for methyl-functionalized material whose hydrophobic surface accelerates the pemetrexed release. The data obtained from release studies were fitted using various kinetic models to determine the pemetrexed release mechanism and its release rate. The best correlations were found for Korsmeyer-Peppas and Higuchi models. Moreover, the theoretical three-parameter model for drug release kinetic was applied to calculate the strength of drug-support interactions. The in vitro cell study was performed on SKBR3 cancer cells and obtained results demonstrated that the modification of the mesoporous silica material by grafted polar/nonpolar groups may significantly affect the compatibility of this material with cells, drug release from this material and subsequent biological activity of PEM.