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

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.


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