Development and in vitro characterization of SLN encapsulating magnetic Heparin coated Iron Oxide for theranostic application

Solid Lipid Nanoparticles (SLN) have been proposed for the oral delivery of drugs with poor oral bioavailability for their ability to be internalized directly by the lymphatic circulation, like chylomicrons, through intestinal absorption. Lymphatic system is considered an interesting target for anti-cancer drugs and contrast agents because exerts an active role in the cancer metastasis being the major route of the solid tumor spread. Recently, according to the potentiality of the iron oxide in diagnostic and of heparin in the cancer therapy, iron oxide nanoparticles non-covalently coated with heparin (Fe@hepa) have been proposed as delivery systems for theranostic application (1). The aim of this work was to encapsulateFe@hepa in a biocompatible solid lipid shell in order to obtain a nanotheranostic tool for promoting the oral absorption through the lymphatic route. SLN have been formulated by a modified self nanoemulsifying technique by using Gelucire50/13 and Geleol™. The resulted Fe@hepa-SLN were characterized regarding size, morphology, storage stability as well in vitro release of heparin and iron oxide. In addition, preliminary studies on Caco-2 cell line were carried out evaluating cytotoxicity by MTT tests and internalization by the direct quantification of Fe@hepa inside the cells. Fe@hepa-SLN displayed a mean diameter below 300 nm, suitable for the oral administration, and an incorporation efficiency of 75% ± 3.9. Morphology analyisis showed the lipid shell surrounding the Fe@hepa nanoparticles and the release studies demonstrated that this lipid envelop stabilized the heparin coating in physiological conditions. Finally, studies on Caco2 cells showed the low cytotoxicity of the Fe@hepa-SLN and their ability to be internalized in the cells used as intestinal permeability model. These results indicate that this novel nanotechnology strategy could be a promising tool for oral nanotheranostic approaches.