Biodegradable magnetic microspheres for drug targeting, temperature controlled drug release, and hyperthermia

Abstract

Magnetic microspheres (MMS) used for magnetic drug targeting consist of magnetic nanoparticles (MNP) and a pharmaceutical agent embedded in a polymeric matrix material. The application of MNP for drug targeting enables guiding the MMS to a target area, imaging the position of the MMS with magnetic particle imaging, and finally inducing drug release. As latter takes place by degradation of the MMS or diffusion through the matrix, an increase in temperature, e.g. through magnetic hyperthermia, leads to an accelerated drug release. Here, MMS consisting of poly(lactic-coglycolic) acid (PLGA) with different monomer ratios were prepared by an oil-in-water emulsion evaporation method. The model drug Camptothecin (CPT) and magnetic multicore nanoparticles (MCNP) with a high specific heating rate were embedded into the microspheres. We obtained MMS in the preferred size range of 1 to 2 μm with a concentration of MCNP of 16wt%, a drug load of about 0.5wt% and an excellent heating performance of 161 W/gMMS. Investigations of the drug release behaviour showed an accelerated drug release when increasing the temperature from 20 °C to 37 °C or 43 °C by using a water bath. In addition, an increase in drug release of about 50% through magnetic heating of the MMS up to 44 °C compared to 37 °C was observed. By this, a magnetic hyperthermia induced CPT release from PLGA MMS is demonstrated for the very first time.

Micro/Nanosystems for Magnetic Targeted Delivery of Bioagents

“…Zahn et al, instead, prepared PLGA microspheres loaded with magnetic multicore NPs and the anticancer drug Camptothecin to investigate the hyperthermia-induced drug release [357]. SAR measurements showed a promising heating power of the microspheres (161 W/g) that led to the release of around 80% Camptothecin at 43 • C. Similar results were obtained by Zhang et al who used nano-in-micro thermo-responsive microspheres loaded with Methotrexate or 5-Fluorouracil [387].…”

“…However, nanosystems were not the only systems to be developed for MPI. In fact, certain magnetic microcarriers have also found applications as MPI agents [357]. Zahn et al designed magnetic microspheres with a size that could be tuned between 1 and 2 µm, which displayed MNPs onto the surface [358].…”

Fundamentals and utilization of solid/ liquid phase boundary interactions on functional surfaces

“…Moreover, numerous drug formulations exploit stimulus-responsivity in order to achieve the controlled release of different active pharmaceutical ingredients (APIs) in a specific target organ and/or at a specific rate [120]. Most examples are pH-or thermoresponsive release systems, where the release is controlled by the pH-or temperature regulated swelling of the drug carrier [121], however, cases of magnetic field-responsivity are also known, which property could be elaborated through the addition of different magnetic particles, such as magnetite (Fe3O4) or maghemite (Fe2O3) [122]. Stimulus-responsivity also opened new perspectives at the field of analytics, where the responsivity serves as a core mechanism in sensing physical quantities, such as pH and temperature [123] and at microfluidics, where these surfaces are used as miniaturized actuators to create and maintain fluid motion via mechanical response or via the altered surface wetting characteristics [124,125].…”

Degradation-Dependent Controlled Delivery of Doxorubicin by Glyoxal Cross-Linked Magnetic and Porous Chitosan Microspheres

“…Magnetically triggered drug release from polymer/nanoparticles has been widely accepted as both bioavailability and therapeutic efficacy can be tuned with better control due to intrinsic magnetic targeting. ,,, Superparamagnetic materials are devoid of complications related to agglomeration, as they possess no net magnetic moment in the absence of an external magnetic field and hence are the most suited option for targeting purposes . Superparamagnetic materials, particularly superparamagnetic iron oxide nanoparticles (SPIONs) with high magnetization, provide good dispersion stability and enable easy separation or targeting of the particles with the aid of an external magnetic field .…”