Design of PEG-modified magnetic nanoporous silica based miltefosine delivery system: Experimental and theoretical approaches

Silica nanoparticles incorporating magnetic iron oxides (MS) with sizes around 20 nm were developed. The MS material was modified with NH2-groups and then grafted by PEG chains. The anticancer drug miltefosine was loaded into the NH2-modified and PEGylated MS nanoparticles by impregnation procedure resulting in 11-28% of drug content. PEG chains were also conjugated to the miltefosine loaded MS-NH2 nanocarrier. The amount of loaded drug and the release properties depend on whether PEGylation of the nanoparticles was performed before or after the drug loading step. The parent and drug loaded samples were characterized by XRD, N-2 physisorption, thermal gravimetric analysis, magnetic measurements, XPS and ATR FT-IR spectroscopy. ATR FT-IR spectroscopic data and DFT calculations supported the interaction between the mesoporous silica surface and miltefosine molecules. The in vitro release profile at pH = 7.0 showed sustained drug release and dependence on the experimental design. Free and formulated miltefosine samples were further investigated for antiproliferative activity against malignant HUT-78 cell line. Formulated miltefosine showed superior cytotoxic effect on the tested cells as compared to the free drug. In addition, the MTT assay of the cytotoxic potential of non-loaded silica nanocomposites showed no intrinsic cytotoxicity associated with the carriers.

Automated summary

Silica nanoparticles incorporating magnetic iron oxides (MS) with sizes around 20 nm were developed for loading the anticancer drug miltefosine, showing potential antiproliferative activity. PEG chains were conjugated to enhance drug loading and release properties. Formulated miltefosine displayed superior cytotoxic effect compared to free drug, with no intrinsic cytotoxicity associated with non-loaded silica nanocomposites.