On the Mechanism of Drug Release from Polysaccharide Hydrogels Cross-Linked with Magnetite Nanoparticles by Applying Alternating Magnetic Fields: the Case of DOXO Delivery

The chemical, biological and physical properties of carboxymethylcellulose (CMC) hydrogels with silanized magnetite (Fe3O4) nanoparticles (NPs) as cross-linker were investigated and compared with the analogous hydrogel obtained by using 1,3-diaminopropane (DAP) as cross-linker. The magnetic hydrogel was characterized from the chemical point of view by FT-IR, whereas the morphology of the hydrogel was investigated by FESEM and STEM. The water uptake and rheological measurements reveal how much the swelling and mechanical properties change when CMC is cross-linked withsilanized magnetite NPs instead of with DAP. As far as the biological properties, the hybrid hydrogel neither exerts any adverse effect nor any alteration on the cells. The magnetic hydrogels show magnetic hysteresis at 2.5 K as well as at 300 K. Magnetic measurements show that the saturation magnetization, remanent magnetization and coercive field of the NPs are not influenced significantly by the silanization treatment. The magnetic hydrogel was tested as controlled drug delivery system. The release of DOXO from the hydrogel is significantly enhanced by exposing it to an alternating magnetic field. Under our experimental conditions (2 mT and 40 kHz), no temperature increase of the hydrogel was measured, testifying that the mechanism for the enhancement of drug release under the AMF involves the twisting of the polymeric chains. A static magnetic field (0.5 T) does not influence the drug release from the hydrogel, compared with that without magnetic field.