A pH-sensitive magnetic hydrogel nanocomposite based on alginate for controlled release of methotrexate

Abstract

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).