Magnetic Drug Targeting: Preclinical in Vivo Studies, Mathematical Modeling, and Extrapolation to Humans

A sound
theoretical rationale for the design of a magnetic nanocarrier
capable of magnetic capture in vivo after intravenous administration
could help elucidate the parameters necessary for in vivo magnetic
tumor targeting. In this work, we utilized our long-circulating polymeric
magnetic nanocarriers, encapsulating increasing amounts of superparamagnetic
iron oxide nanoparticles (SPIONs) in a biocompatible oil carrier,
to study the effects of SPION loading and of applied magnetic field
strength on magnetic tumor targeting in CT26 tumor-bearing mice. Under
controlled conditions, the in vivo magnetic targeting was quantified and found to be directly proportional
to SPION loading and magnetic field strength. Highest SPION loading,
however, resulted in a reduced blood circulation time and a plateauing
of the magnetic targeting. Mathematical modeling was undertaken to
compute the in vivo magnetic, viscoelastic, convective, and diffusive
forces acting on the nanocapsules (NCs) in accordance with the Nacev–Shapiro
construct, and this was then used to extrapolate to the expected behavior
in humans. The model predicted that in the latter case, the NCs and
magnetic forces applied here would have been sufficient to achieve
successful targeting in humans. Lastly, an in vivo murine tumor growth
delay study was performed using docetaxel (DTX)-encapsulated NCs.
Magnetic targeting was found to offer enhanced therapeutic efficacy
and improve mice survival compared to passive targeting at drug doses
of ca. 5–8 mg of DTX/kg. This is, to our knowledge, the first
study that truly bridges the gap between preclinical experiments and
clinical translation in the field of magnetic drug targeting.