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Magnetically-assisted delivery of therapeutic agents to the site of interest, which is referred to as magnetic drug targeting, has proven to be a promising strategy in a number of studies. One of the key advantages over other targeting strategies is the possibility to control remotely the distribution and accumulation of the nanocarriers after parenteral administration. However, preparation of effective and robust magnetically responsive nanocarriers based on superparamagnetic iron oxide nanocrystals (SPIONs) still represents a great scientific challenge, since spatial guidance of individual SPIONs is ineffective despite the presence of high magnetic field gradient. A strategy to overcome this issue is the clustering of SPIONs to achieve sufficient magnetic responsiveness. In this mini-review, we address current and future strategies for the design and fabrication of magnetically responsive nanocarriers based on SPIONs for magnetically-targeted drug delivery, including the underlying physical requirements, the possibility of drug loading, and the control of drug release at the targeted site.

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The development of various magnetically-responsive nanostructures is of great importance in biomedicine. The controlled assembly of many small superparamagnetic nanocrystals into large multi-core clusters is needed for effective magnetic drug delivery. Here, we present a novel one-pot method for the preparation of multi-core clusters for drug delivery (i.e., magnetic nanocarriers). The method is based on hot homogenization of a hydrophobic phase containing a nonpolar surfactant into an aqueous phase, using ultrasonication. The solvent-free hydrophobic phase that contained tetradecan-1-ol, γ-Fe2O3 nanocrystals, orlistat, and surfactant was dispersed into a warm aqueous surfactant solution, with the formation of small droplets. Then, a pre-cooled aqueous phase was added for rapid cooling and the formation of solid magnetic nanocarriers. Two different nonpolar surfactants, polyethylene glycol dodecyl ether (B4) and our own N1,N1-dimethyl-N2-(tricosan-12-yl)ethane-1,2-diamine (SP11), were investigated for the preparation of MC-B4 and MC-SP11 magnetic nanocarriers, respectively. The nanocarriers formed were of spherical shape, with mean hydrodynamic sizes <160 nm, good colloidal stability, and high drug loading (7.65 wt.%). The MC-B4 nanocarriers showed prolonged drug release, while no drug release was seen for the MC-SP11 nanocarriers over the same time frame. Thus, the selection of a nonpolar surfactant for preparation of magnetic nanocarriers is crucial to enable drug release from nanocarrier.