Synthesis, characterization and pH-controllable methotrexate release from biocompatible polymer/silica nanocomposite for anticancer drug delivery

Abstract

The objective of this study was to develop pH-responsive silica nanoparticles by imidazole-based ionic liquid for controlled release of methotrexate. In this article, we synthesized pH-responsive cationic silica nanoparticles by graft copolymerization of vinyl functionalized silica nanoparticles and methacrylic acid (MAA) monomer. Imidazole-based ionic liquid (Im-IL) was verified by (HNMR)-H-1 and Fourier-transform infrared (FTIR) spectroscopy. The synthesized functionalized silica particles were characterized and confirmed by various technologies including the scanning electron microscopy (SEM), the infrared spectroscopy (IR) and the thermogravimetric analysis (TGA). SEM results reveal the uniformity in size/ shape of silica particles. This nanosystem is modified for targeted delivery of an anticancer agent methotrexate. The nanocomposite-MTX complex was formed at physiological pH (7.4) due to the electrostatic interactions between anionic carboxylic group of MTX molecules and cationic rings in carrier, while, the release of which can be achieved through the cleavage of the nanocomposite-MTX complex by protonation of carboxyl groups in the MTX segment that are sensitive to variations in external pH at weak acidic conditions. FT-IR spectroscopy showed the presence of light interactions between the silicate silanols and the drug. MCF7 cells were incubated with the MTX-free nanocomposite and MTX-loaded nanocomposite at various concentrations for 24, 48 and 72 h, and the data showed that the nanocomposites themselves did not affect the growth of MCF7 cells. Antitumor activity of the MTX-loaded nanocomposites against the cells was kept over the whole experiment process. The results showed that the MTX could be released from the fibers without losing cytotoxicity.