Department of Chemistry, Aristotle University of Thessaloniki , 54124 Thessaloniki, Greece.
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki , 54124 Thessaloniki, Greece.
ACS Appl Mater Interfaces. 2016 Apr 13;8(14):9345-60. doi: 10.1021/acsami.6b00408. Epub 2016 Mar 29.
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, (1)H NMR, (13)C 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, (99m)Tc. 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 (99m)Tc-MNPs@NAP carriers showed increased accumulation at the inflammation site.
磁性纳米粒子（MNPs）可以通过分布到靶向区域在磁性药物输送中发挥独特的作用。此类 MNPs 的制备是一项具有挑战性的多重任务，需要优化尺寸、磁性和表面特性，以实现理想的靶向选择性，同时保持药物持续释放作为前提。在这种情况下，通过在十八胺（ODA）存在下溶剂热合成了具有小尺寸（约 7nm）和中等饱和磁化强度（约 60 emu g(-1)）的 CoFe2O4 MNPs，以研究功能化途径对药物释放的影响。合成规律允许我们制备具有氨基化（AmMNPs）和无氨基（FAmMNPs）表面的 MNPs。通过直接与 ODA 上的 NH2 基团偶联，将具有羧酸盐供体的非甾体抗炎药萘普生（NAP）添加到 AmMNPs 中，形成酰胺键。对于 FAmMNPs，通过中间连接体（聚乙烯亚胺）和 PEG 化 MNPs 进行间接偶联 NAP。FT-IR、（1）H NMR、（13）C NMR 和 UV-vis 数据证实了 NAP 的加入，而不同的功能化方法观察到不同的药物释放行为。在用 γ 发射放射性核素（99m）Tc 标记后，在体外在大鼠血清中和体内在小鼠中评估了 MNPs@NAP 的生物学行为。MNPs@NAP 载体的体内命运与 NAP 的直接或间接偶联直接相关。此外，在肌肉内诱导炎症，其中直接偶联的（99m）Tc-MNPs@NAP 载体在炎症部位显示出增加的积累。
