Rotating Magnetic Nanoparticle Clusters as Microdevices for Drug Delivery

Abstract

Alexander J Willis,1 Sebastian P Pernal,2 Zachary A Gaertner,3 Sajani S Lakka,1 Michael E Sabo,4 Francis M Creighton,4 Herbert H Engelhard5 1Division of Hematology-Oncology, Department of Medicine, The University of Illinois at Chicago, Chicago, IL, USA; 2Wayne State University, Detroit, MI, USA; 3Northwestern University, Chicago, IL, USA; 4Pulse Therapeutics, Inc, St. Louis, MO, USA; 5Departments of Neurosurgery and Bioengineering, The University of Illinois at Chicago, Chicago, IL, USACorrespondence: Herbert H EngelhardThe University of Illinois at Chicago, 912 South Wood St., Chicago, IL 60612, USATel [phone]Email [email protected]: Magnetic nanoparticles (MNPs) hold promise for enhancing delivery of therapeutic agents, either through direct binding or by functioning as miniature propellers. Fluid-filled conduits and reservoirs within the body offer avenues for MNP-enhanced drug delivery. MNP clusters can be rotated and moved across surfaces at clinically relevant distances in response to a rotating magnet. Limited data are available regarding issues affecting MNP delivery by this mechanism, such as adhesion to a cellular wall. Research reported here was initiated to better understand the fundamental principles important for successful implementation of rotational magnetic drug targeting (rMDT).Methods: Translational movements of four different iron oxide MNPs were tested, in response to rotation (3 Hz) of a neodymium–boron–iron permanent magnet. MNP clusters moved along biomimetic channels of a custom-made acrylic tray, by surface walking. The effects of different distances and cellular coatings on MNP velocity were analyzed using videography. Dyes (as drug surrogates) and the drug etoposide were transported by rotating MNPs along channels over a 10 cm distance.Results: MNP translational velocities could be predicted from magnetic separation times. Changes in distance or orientation from the magnet produced alterations in MNP velocities. Mean velocities of the fastest MNPs over HeLa, U251, U87, and E297 cells were 0.24 ± 0.02, 0.26 ± 0.02, 0.28 ± 0.01, and 0.18 ± 0.03 cm/sec, respectively. U138 cells showed marked MNP adherence and an 87.1% velocity reduction at 5.5 cm along the channel. Dye delivery helped visualize the effects of MNPs as microdevices for drug delivery. Dye delivery by MNP clusters was 21.7 times faster than by diffusion. MNPs successfully accelerated etoposide delivery, with retention of chemotherapeutic effect.Conclusion: The in vitro system described here facilitates side-by-side comparisons of drug delivery by rotating MNP clusters, on a human scale. Such microdevices have the potential for augmenting drug delivery in a variety of clinical settings, as proposed.Keywords: etoposide, glioblastoma, iron oxide nanoparticles, in vitro model, lung cancer, magnetic drug targeting, nanodevice

Keywords

• etoposide
• glioblastoma
• iron oxide nanoparticles
• in vitro model
• lung cancer
• magnetic drug targeting
• nanodevice