Magnetically Guided Targeted Drug Delivery System of Erythropoietin Using Magnetic Nanoparticles: Proof of Concept

Abstract

Purpose: The objective of this proof-of-concept study was to demonstrate the targeted delivery of erythropoietin (EPO) using magnetically guided magnetic nanoparticles (MNPs). Materials and Methods: MNPs consisting of a ferric-ferrous mixture (FeCl36H2O and FeCl24H2O) were prepared using a co-precipitation method. The drug delivery system (DDS) was manufactured via the spray-drying technique using a nanospray-dryer. The DDS comprised 7.5 mg sodium alginate, 150 mg MNPs, and 1000 IU EPO. Results: Scanning electron microscopy revealed DDS particles no more than 500 nm in size. Tiny particles on the rough surfaces of the DDS particles were composed of MNPs and/or EPO, unlike the smooth surfaces of the only alginate particles. Fourier-transform infrared spectroscopy revealed DDS peaks characteristic of MNPs as well as of alginate. Standard soft lithography was applied to DDS particles prepared with fluorescent beads using a microchannel fabricated to have one inlet and two outlets in a Y-shape. The fluorescent DDS particles reached only one outlet reservoir in the presence of a neodymium magnet. The neurotoxicity was evaluated by treating SH-SY5Y cells in 48-well plates (1 X 105 cells/well) with 2 L of a solution containing sodium alginate (0.075 mg/mL), MNPs (1.5 mg/mL), or sodium alginate + MNPs. A cell viability assay kit was used to identify a 93% cell viability after MNP treatment and a 94% viability after sodium alginate + MNP treatment, compared with the control (p < 0.01). Conclusions: The DDS-EPO construct developed here can be guided using magnetic control without displaying significant neurotoxicity.