Interest in the design of new drug delivery systems focuses on releasing the drug at a controlled rate and desired time. Magnetic nanoparticles (MNPs) have shown great potential for use in biomedicine due to their ability to get close to biological entities such as cells, viruses, proteins, and genes with heating ability when exposed to a time-varying magnetic field. Superparamagnetic MNPs with proven biocompatibility have attracted attention as drug carriers in hyperthermia therapy, magnetic resonance imaging (MRI) as a contrasting agent, tissue repair, immunoassay, and cell separation procedures.

To potentially use MNPs in biomedical fields and to understand their implications, it is essential to develop a generic synthetic route that can transfer MNPs from an organic phase to an aqueous phase. The present work has developed a novel route for the synthesis of the aqueous-phase dispersible MNPs coated with the thermoresponsive polymer poly(NIPAAm). It is believed that this novel route for the synthesis of the thermoresponsive core-shell MNPs in aqueous medium will prove a potential step forward in the use of these core-shell MNPs in robust controlled drug delivery, tissue repair, immunoassay, cell separation, biomagnetic separation of biomolecules, etc.

AC magnetic field produces magnetic rotations or alignments in response to a high-frequency magnetic field, allowing nanoparticles to heat up the surrounding hydrogel matrix in which they are trapped. Such remote heating could be used for inducing noninvasive focused hyperthermia, for controlled drug release, and for triggering thermosensitive changes in hydrogel volume or shape. Magnetic hydrogels thus offer ways to selectively target, detect, and potentially treat cancer tissue via magnetic resonance imaging (MRI) and inductive heating.

Hybrid materials can be obtained by combining metal-based nanoparticles, e.g., gold (Au), silver (Ag), and iron (Fe), with polymer hydrogels for the synthesis of stable film formation. There is small effect on the mechanical properties of the resulting nanocomposite hydrogels by the addition of metallic nanoparticles as far as the interactions between polymer and nanoparticles are weak. Stronger polymer–nanoparticle interactions that are induced, e.g., by the attachment of gold reactive thiol groups to the poly(NIPAAm) hydrogel, may alter the thermosensitivity and swelling behavior. Using gold and silver, other nanoparticles such as iron, cobalt (Co), nickel (Ni), copper (Cu), and also metal alloys, salts, and metal-derived quantum dots (2–100 nm) can be mixed with or synthesized within a hydrogel matrix. The applications of these hydrogels can be found in catalysis, sensors, actuators, and microfluidic devices, and also in separation technology. However, only nontoxic and nonhazardous biomaterials will find usage in the pharmaceutical and medical fields.

To obtain the OA-modified MNPs (OA-MNPs), calculated amounts of MNPs were sonicated in deionized water for 1 hour, after which 13 mL of OA per gram of MNPs were added dropwise into the MNP-dispersed water at 80 ºC over the course of two hours under vigorous mechanical stirring and nitrogen atmosphere. After modification, the MNPs were extracted into n-hexane and washed repeatedly with first water and then ethanol to remove the unreacted OAs.

The introduction of MAH in β-CD was performed according to the following method. A 5.68 g of β-CD (0.005 mol) was dissolved in 30 mL DMF, and then 4.90 g of MAH (0.05 mol) was added to it. The solution was heated at 80 ºC under vigorous stirring for 10 hours. When the reaction was completed, the solution was cooled at room temperature and 30 mL of trichloromethane were added to it. White precipitates of MAH-β-CD were filtered, washed three times with acetone, dried in a vacuum oven at 40 ºC for 24 hours, and stored in a glass vial. For the coating of the OAMNPs with MAH-β-CD (MAH-β-CD-MNPs), equal volumes of the OA-MNPs n-hexane solution (2 wt %) and the MAH-β-CD aqueous solution (2 wt %) were mechanically stirred at room temperature for 48 hours.

The OA-MNPs were transferred into the MAH-β-CD aqueous solution to make the MAH-β-CD-MNPs. The MAH- β-CD-MNP powders were obtained by drying the aqueous part of the phaseseparated n-hexane/water solution. The MAH-β-CD-MNPs were used to make the thermoresponsive core-shell MNPs that consist of the magnetite core and the poly(NIPAAm) shell (poly(NIPAAm)- MNPs) by using a precipitation polymerization method in the presence of KPS (as an initiator) and MBA (as a crosslinker) under nitrogen atmosphere at 70 ºC. The mixture was cooled to room temperature and diluted with distilled water. The poly(NIPAAm)-MNPs were isolated from the solution by placing a magnet below the reaction vial. This process was repeated several times to remove the unreacted NIPAAm monomers and the separated poly (NIPAAm) chains from the MNPs.

Apart from aqueous dispersible thermoresponsive MNPs, a composite film of PNIPAAm and magnetite can also be made by using the photoinitiator as APS and UV irradiation, which can show thermoresponsive property in AC magnetic field.

This work was done by Soo-Young Park of Kyungpook National University, Korea, for the Air Force Research Laboratory’s Asian Office of Aerospace Research and Development. AFRL-0185

Medical Design Briefs Magazine

This article first appeared in the May, 2012 issue of Medical Design Briefs Magazine.

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