Octadecylamine-Mediated Versatile Coating of CoFe₂O₄ NPs for the Sustained Release of Anti-Inflammatory Drug Naproxen and in Vivo Target Selectivity

Magnetic nanoparticles (MNPs) can play a distinct role in magnetic drug delivery via their distribution to the targeted area. The preparation of such MNPs is a challenging multiplex task that requires the optimization of size, magnetic, and surface properties for the achievement of desirable target selectivity, along with the sustained drug release as a prerequisite. In that context, CoFe2O4 MNPs with a small size of ∼7 nm and moderate saturation magnetization of ∼60 emu g–1 were solvothermally synthesized in the presence of octadecylamine (ODA) with a view to investigate the functionalization route effect on the drug release. Synthetic regulations allowed us to prepare MNPs with aminated (AmMNPs) and amine-free (FAmMNPs) surface. The addition of the nonsteroidal anti-inflammatory drug with a carboxylate donor, Naproxen (NAP), was achieved by direct coupling with the NH2 groups, rendered by ODA, through the formation of an amide bond in the case of AmMNPs. In the case of FAmMNPs, indirect coupling of NAP was performed through an intermediate linker (polyethylenimine) and on PEG-ylated MNPs. FT-IR, 1H NMR, 13C NMR, and UV–vis data confirmed the addition of NAP, whereas diverse drug-release behavior was observed for the different functionalization approaches. The biological behavior of the MNPs@NAP was evaluated in vitro in rat serum and in vivo in mice, after radiolabeling with a γ-emitting radionuclide, 99mTc. The in vivo fate of MNPs@NAP carriers was in straightforward relation with the direct or indirect coupling of NAP. Furthermore, an inflammation was induced intramuscularly, where the directly coupled 99mTc-MNPs@NAP carriers showed increased accumulation at the inflammation site

Development and Pharmacological Evaluation of New Bone-Targeted ^99mTc-Radiolabeled Bisphosphonates

A novel bisphosphonate, 1-(3-aminopropylamino)­ethane-1,1-diyldiphosphonic acid (<b>3</b>), was coupled to the tridentate chelators di-2-picolylamine, 2-picolylamine-<i>N</i>-acetic acid, iminodiacetic acid, 3-((2-aminoethyl)­thio)-3-(1<i>H</i>-imidazol-4-yl)­propanoic acid, and 2-((2-carboxyethyl)­thio)-3-(1<i>H</i>-imidazol-4-yl)­propanoic acid to form ligands <b>6</b>, <b>9</b>, <b>11</b>, <b>15</b>, and <b>19</b>, respectively. Organometallic complexes of the general formula [Re/^99mTc­(CO)₃(κ³-L)] were synthesized, where L denotes ligand <b>6</b>, <b>9</b>, <b>11</b>, <b>15</b>, or <b>19</b>. The rhenium complexes were prepared at the macroscopic level and characterized by spectroscopic methods. The technetium-99m organometallic complexes were synthesized in high yield and were identified by comparative reversed-phase HPLC with their Re analogues. The ^99mTc tracers were stable <i>in vitro</i> and exhibited binding to hydroxyapatite. In biodistribution studies, all of the ^99mTc complexes exhibited high bone uptake superior to that of <b>25</b>, which is the directly ^99mTc-labeled bisphosphonate <b>3</b>, and comparable to that of ^99mTc-methylene diphosphonate (^99mTc-MDP). The tracers [^99mTc­(CO)₃(<b>6</b>)] (<b>26</b>), [^99mTc­(CO)₃(<b>9</b>)] (<b>27</b>), [^99mTc­(CO)₃(<b>11</b>)] (<b>28</b>), and [^99mTc­(CO)₃(<b>15</b>)] (<b>29</b>) exhibited higher bone/blood ratios than ^99mTc-MDP. <b>26</b> had the highest bone uptake at 1 h p.i. The new bisphosphonates showed no substantial growth inhibitory capacity in PC-3, Saos-2, and MCF-7 established cancer cell lines at low concentrations. Incubation of <b>26</b> with the same cancer cell lines indicated a rapid and saturated uptake. The promising properties of <b>26</b>–<b>29</b> indicate their potential for use as bone-imaging agents