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Abstract
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The aim of this study is the synthesis of pH-responsive cationic silica nanoparticles (NPs) by pyridinium-based ionic liquid
for the improved sustained release formulations of methotrexate (MTX) as an anionic anticancer drug. Fanctionalized
cationic silica NPs were successfully prepared via graft copolymerization of methacrylic acid (MAA) onto vinyl-bond-modified
silica NPs. The prepared NPs were characterized using the scanning electron microscopy (SEM), the infrared spectroscopy
(IR), and the thermogravimetric analysis. The resultant NPs were uniform spherical NPs with a mean diameter of
approximately 160 ± 20 nm. We explored the ionic interaction of MTX NPs in order to generate pH-responsive controlled
release system. The cumulative release of MTX-loaded composite microspheres shows a highly desirable precise
pH-responsive drug release performance, i.e. loaded drug would not leak in physiological pH (7.4), but would release in a
sustained way, where the pH value is lower (4). The protonation of carboxyl groups at mildly acidic condition resulted in a
faster dissociation of copolymer/MTX complex, leading to an accelerated release of MTX at pH 4. Thus, complexation of
MTX with NPs yielded a drug delivery system affording a pH-triggered release of MTX in an acidic environment. The
in vitro cytotoxicity test by MTT assay against breast cancer cells, MCF7 indicates that NPs are nontoxic and suitable to
use as drug carriers. 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 nanocomposites without losing cytotoxicity
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