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

Abstract

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 with silanized 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.

Monitoring Endothelial and Tissue Responses to Cobalt Ferrite Nanoparticles and Hybrid Hydrogels

“…The groups could react with the carboxylic acid groups of the polysaccharide, forming amido groups. NPs in the aqueous dispersions and inside the hydrogels form aggregates with an average size around 100 nm [11]. The weight of NPs constitutes 50% of the weight of the polymer, since the crosslinking reaction that leads to NPs-CMC formation, performed with less than 50% NPs does not lead to the formation of a stable hydrogel.…”

“…Previous research led to synthesis of a magnetic hybrid polysaccharide hydrogel that could release a drug when alternate magnetic fields (AMF) were applied [9, 10, 11]. The organic part is a carboxymethylcellulose (CMC) polymer and the inorganic part consists of cobalt-ferrite (CoFe 2 O 4 ) NPs coated with (3-aminopropyl)trimethoxysilane (APTMS) to obtain CoFe 2 O 4 -NH 2 NPs.…”

Magnetic Gel Composites for Hyperthermia Cancer Therapy

“…Barbucci and co-workers [52,53] reported the preparation of new non-toxic hybrid hydrogels based on the covalent binding of magnetic CoFe 2 O 4 magnetic nanoparticles to carboxymethylcellulose (CMC). The nanoparticles were first functionalized with (3-aminopropyl)-trimethoxysilane (APTMS) in order to introduce amino groups on the surface (the magnetic properties of the nanoparticles are not influenced significantly by the silanization treatment [54]). Subsequent EDC coupling with the carboxylic groups of CMC yielded the corresponding hybrid biomaterial (Figure 6, top ).…”

“…Very interestingly, no heating effect on the sample was apparently observed in this case, suggesting the possibility of a different release mechanism. However, hyperthermic properties were observed at higher frequency and field amplitude [54]. Additional experiments using composites with different amounts of magnetic nanoparticles ( i.e.…”

“…The reaction involves the formation of an amide bond between the carboxylic groups of CMC and the amine groups of the amino-functionalized metal oxide nanoparticles (cross-linkers) in the presence of EDC and NHS; Bottom : Ball-and-stick molecular model of DOX (doxorubicin) and comparison of its release from Fe 3 O 4 -CMC hydrogel composite in NaCl 0.15 M in the absence of magnetic field (circles), in the presence of an AMF (squares) and with SMF (triangles). Adapted with permission from reference [52] and reference [54]. Copyrights © 2011 Royal Society of Chemistry and © 2015 MDPI, respectively.…”