Gadolinium incorporated reconstituted chylomicron emulsion for potential application in tumor neutron capture therapy

Abstract

Gadolinium (Gd) neutron capture therapy (NCT) is currently under development as a potential approach for tumor therapy. Nanoparticles have been suggested as a potential delivery system to carry or target Gd to tumors for thermal or epithermal neutron irradiation. The reconstituted chylomicron emulsion is an artificial chylomicron remnant prepared using commercially available natural and biocompatible lipids. We proposed to use this nanometer-scale emulsion to deliver Gd to solid tumors by modifying the surface of the emulsion. A lipophilic Gd compound, gadolinium acetylacetonate (GdAcAc), was incorporated into the emulsion, resulting in a final pure Gd concentration of more than 1 mg/mL. The apparent solubility of GdAcAc was enhanced by about 6000-fold by this incorporation. The emulsion particles were shown to be stable in a two-week short-term stability study when stored at 4 °C. In addition, no extensive particle aggregation was observed when the emulsion particles were incubated in simulated biological media such as serum. Also, GdAcAc does not significantly ‘leak’ out from the emulsion particles. Only ∼5% was released in 20 h in a SDS (0.5% w/v) in phosphate buffered saline (pH 7.4, 10 mM) medium. Finally, the emulsion particles were coated with polyethylene glycol (PEG), and injected into Balb/C mice via the tail vein. A significant proportion (71.6±18.4%) of the PEG-coated, GdAcAc-incorporated emulsion remained circulating in the blood 5 h after the injection, while the PEG-free emulsion was mainly accumulated inside the liver. This chylomicron emulsion may be used to deliver Gd into solid tumors for NCT.