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.
Highlights
The synthesis of magnetic hybrid hydrogels consists of two important steps, as already described for the analogous CMC-NPs (CoFe2O4) hydrogel [24]: a) functionalization of the magnetite (Fe3O4) NPs with APTMS in order to introduce -NH2 groups on the NPs surface (NPs-NH2); and b) binding of CMC polymer to the (Fe3O4) NPs-NH2, via the formation of an amide bond between the CMC carboxylic groups and the -NH2 groups on the NPs surface in order to get the hybrid hydrogel
The size and polydispersity index (PDI) of the aggregates formed by NPs-NH2 (Fe3O4) are smaller than those of the aggregates formed by bare NPs
We investigated hydrogels with magnetic (Fe3O4) NPs used as cross-linkers of polysaccharide chains
Summary
Magnetic nanoparticles (NPs) have been evaluated extensively for local delivery of pharmaceuticals via magnetic drug targeting [1,2,3,4,5,6] and via attachment of high affinity ligands [7,8,9].while offering an attractive mean for remotely directing therapeutic agents to a diseased site, the magnetic NPs simultaneously reduce dosage and deleterious side effects associated with non-specific uptake of cytotoxic drugs by healthy tissues [10,11,12,13,14,15,16,17]. Specific antibodies can be conjugated to the magnetic NPs to bind selectively to related receptors and inhibit tumor growth; magnetic NPs can be used for hyperthermia and for targeted delivery of antitumor agents adsorbed on their surface [18,19,20,21]. The small size of NPs induces researchers to utilize large amount of them to get an appreciable quantity of drug in the diseased site, their presence in the organism, especially in large amount, is certainly to be avoided. To overcome this health issue, NPs can be enclosed into the polysaccharide matrix of a hydrogel. Other intrinsic characteristics of hydrogels are the low cost, excellent biocompatibility, the possibility of chemical functionalization and last but not the least, the possibility to entrap large quantity of drug [22,23]
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