Magnetic investigation of iron oxide loaded lipid nanodroplets for drug delivery

Recently, iron oxide magnetic nanoparticles (MNPs) have been the subject of an intense research activity, regarding in particular their use for the treatment of cancer. With this respect, different scenarios can be envisaged, e.g. the delivery of drugs by using MNPs as vehicles under the influence of a static magnetic field or the thermally activated release of drugs thanks to the heat produced by the MNPs in presence of an alternating magnetic field. In this view, and to improve the biocompatibility and in vivo stability of the MNPs, they may be embedded in a biocompatible shell carrying a specific drug [1]. In this contribution, we present a preliminary study concerning the feasibility of the production of magnetic lipid nanodroplets, consisting of an aggregate of lipid molecules and MNPs, for biomedical applications. MNPs were obtained by a precipitation method; afterwards, different experimental protocols and lipid mixtures were used to produce magnetic lipid nanodroplets. Two types of lipid nanodroplets were obtained, namely solid lipid nanodroplets (SLN) and nanostructured lipid nanodroplets (NLN). SLN of stearic acid were produced by emulsion followed by dilution method while NLN, alternatively composed of a mixture of tristearin / tricaprylin or tristearin / labrasol / phosphatidylcholine, were produced by homogenization followed by ultrasonication method. MNPs, with a 5 % relative mass concentration, were added to the lipid phase before the emulsion formation. The samples were characterized using photon correlation spectroscopy and X-ray diffraction. Magnetization loops at different temperatures (Ts) and magnetization vs. T curves, in the zero field cooling and field cooling modes [2], were collected in the 6 K – 300 K range with a SQUID magnetometer. MNPs were also analyzed using transmission Mössbauer spectroscopy in the 25 K – 300 K temperature range with a 57Co in Rh source. For what concerns the as-prepared MNPs, the 25 K Mössbauer spectrum showed just one sextet with a hyperfine field of ~ 50 kOe. This result, and the absence of sextet asymmetries, expected even for small size magnetite nanoparticles, suggests that MNPs are possibly made of maghemite [3]. At T = 6 K, their saturation magnetization was ~ 33 emu/g, about 40 % of the value of bulk maghemite. This effect may be due to the presence of crystalline disorder and/or to the canting of surface spins [2]. The size analysis performed by photon correlation spectroscopy showed that SLN are larger than NLN, being their average size equal to 500 nm and 200 nm, respectively, but monodispersed and stable up to ten months. The X-Ray diffraction spectra indicated that the MNPs nanocrystalline structure is not affected by the inclusion process within lipid nanodroplets. Apart from a decrease in saturation magnetization, due to the dispersion of MNPs in the lipid fluid, the magnetic properties of both the SLN and the NLN samples do not substantially differ from those of the as-prepared MNPs, indicating that the magnetic interparticle interactions are still present. This suggests that the MN may form agglomerates within the lipid nanoparticles. This study confirms the possibility to incorporate MNPs in lipid nanodroplets; their magnetic and physicochemical properties are in favor their possible use both in therapy and in diagnostics. [1] A. M. G. C. Dias et al. Biotechnol. Adv., 29 (2011) 142. [2] L. Del Bianco et al. Mater. Res. Express. 2 (2015) 065002. [3] J. Tuček et al. J. Nanosci. Nanotechnol. 6 (2006) 926. I. Dézsi et al. J. Appl. Phys. 103 (2008) 104312