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

Abstract

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.

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

“…Magnetic nanoparticles are already versatilely used in research and partly in clinical issues for hyperthermia or drug delivery in tumor [31][32][33][34][35] and infection treatment [36,37], as contrast agents for magnetic resonance imaging [38][39][40], and others [41,42]. The biocompatibility of certain magnetic nanoparticles with different composition, magnetic properties or size has already been published [43,44]. Surface modifications with polyvinyl alcohol, polyethylene glycol (PEG, used in this study) or dextran, among others, can be performed to protect particles from rapid capture out of the bloodstream by the immune system, particularly by the mononuclear phagocyte system (MPS) [45][46][47][48].…”

“…Surface modifications with polyvinyl alcohol, polyethylene glycol (PEG, used in this study) or dextran, among others, can be performed to protect particles from rapid capture out of the bloodstream by the immune system, particularly by the mononuclear phagocyte system (MPS) [45][46][47][48]. Nevertheless, undesired particle uptake into different organs occurs, for example into the lung, liver, and spleen following intravenous administration [43,49] and has to be minimized. To our knowledge, no studies were performed dealing with in vivo extravasation of magnetic nanoparticles towards the surface of the magnetic source.…”

Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications

“…The high sensitivity of liposome to temperature increase, as well as high responsiveness to the localized AC magnetic field led to a simultaneous folate receptor-mediated uptake into tumor cells along with inducing hyperthermia. [645] In a very recent study, Al-Jamal et al [646] utilized long-circulating polymeric magnetic nanocarriers, encapsulating increasing amounts of SPIONs in a biocompatible oil carrier, to study the effects of SPION loading and of applied magnetic field strength Figure 36. Schematic representation of ordered microstructure of superparamagnetic iron oxide nanoparticles and Pluronic F127 copolymers: a) before applying the magnetic field, indomethacin drug molecules are encapsulated in the hydrophobic moiety of micelles; b) upon applying the magnetic field drug releasing is enhanced due to orientation of MNPs and squeezing the micelle.…”

Forecastable and Guidable Bubble‐Propelled Microplate Motors for Cell Transport

“…The motion pattern and speed were compared with analytical and numerical simulations of refs . and the literature …”