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

Abstract

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.

Nanoplatforms of Manganese Ferrite Nanoparticles Functionalized with Anti‐Inflammatory Drugs

“…Nonetheless, appropriate functionalization of the MNPs could result in the design of multifunctional drug carriers, finding applications as contrast agents in magnetic resonance imaging and/or in magnetic hyperthermia , . Even though polymeric nanoparticles and MNPs have been studied in the area of theranostics in the sense that diagnosis coexists with targeted drug and/or gene delivery in case of tumors, the use of MNPs as NSAIDs carriers has been scarcely reported …”

Technetium‐99m radiochemistry for pharmaceutical applications

“…Technetium‐99m labeling usually pertains tagging the radionuclide on the organic material, by direct labeling, via their available donor atoms such as the free amine groups of chitosan, octadecylamine, polyethyleneimine, the carboxylates of poly‐ γ ‐glutamic acid, and poly( d , l ‐lactic‐co‐glycolic acid), as well as the thiol groups of bovine serum albumin. In other examples, the organic material is functionalized with a chelator, such as DTPA . A different labeling method of an iron oxide nanoparticle where a 99m Tc‐bisphosphonate complex was introduced on the iron oxide surface was reported recently .…”

“…In other examples, the organic material is functionalized with a chelator, such as DTPA. [154][155][156][157][158][159][160][161][162] A different labeling method of an iron oxide nanoparticle where a 99m Tc-bisphosphonate complex was introduced on the iron oxide surface was reported recently. 163 In another method, the coating material of the magnetic nanoparticle was conjugated to guanine via glutaraldehyde and was labeled with [ 99m Tc(CO) 3 ] + .…”

Design of Organic Macrocycle‐Modified Iron Oxide Nanoparticles for Drug Delivery

“…Direct coating involves attaching macrocycles to the IONP surface without the use of organic linkers or shell materials. This approach can be challenging because it requires that suitable functionality be present on both the macrocycles and the surface of the particles . However, DDSs that rely on direct coating tend to be easier to fabricate, particularly with CAs and CBs.…”