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Abstract
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Development of a carrier with controlled release manner for methotrexate (MTX), an anticancer
drug with short elimination half-life of 3-10 h, is important to overcome undesired side effects of
conventional systems. This study demonstrated the synthesis of a pH-sensitive magnetic hydrogel
nanocomposite based on montmorillonite (MMT), magnetite (Fe3O4), and alginate (Alg) for
extended release of MTX. MMT-Fe3O4 with different amounts of MMT, were prepared by growth
of Fe3O4 nanoparticles on the surface of MMT. Then, the MMT-Fe3O4-MTX-Alg nanocomposite
beads were prepared by coating of well dispersed MMT-Fe3O4-MTX with Alg. The characterization
was investigated using FTIR, XRD, DLS, FESEM-EDX, TGA, and VSM techniques. By introducing 1 g
of MMT in hydrogel beads, the encapsulation efficiency and loading content were enhanced to
99.34% and 18.71%, respectively. Pure drug exhibits a burst release of 100% within 4 h. Whereas
for MMT (1)-Fe3O4-MTX-Alg, less burst release of 12.4% and 27.6% in the gastric and intestinal
fluid was obtained, respectively within 4 h. This phenomenon leads to the beads remaining intact
passing through the stomach, but the release rate is done at an acceptable rate at the relatively
alkaline environment of the intestine. The release kinetics of MTX from the nanocomposite beads
follows the Korsmeyer-Peppas model. Finally, MTT assay and RT-PCR analysis were followed on
MDA-MB-231 breast cancer cells, to assess their anti-proliferative, apoptotic and antiapoptotic
effects. MMT-Fe3O4-MTX-Alg significantly reduced the percentage of viable cells, with a high
down-regulation in the expression level of the anti-apoptotic gene (Bcl-2), and up-regulation in
the apoptotic gene (Bax).
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