Superparamagnetic Iron Oxide Nanoparticles Encapsulated in Biodegradable Thermosensitive Polymeric Micelles: Toward a Targeted Nanomedicine Suitable for Image-Guided Drug Delivery

Superparamagnetic iron oxide nanoparticles (SPIONs) have been receiving great attention lately due to their various biomedical applications, such as in MR imaging and image guided drug delivery. However, their systemic administration still remains a challenge. In this study, the ability of biodegradable thermosensitive polymeric micelles to stably encapsulate hydrophobic oleic-acid-coated SPIONs (diameter 5-10 nm) was investigated, to result in a system fulfilling the requirements for systemic administration. The micelles were composed of amphiphilic, thermosensitive, and biodegradable block copolymers of poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide dilactate] (mPEG-b-p(HPMAm-Lac2)). The encapsulation was performed by addition of one volume of SPIONs in THF to nine volumes of a cold aqueous mPEG-b-p(HPMAm-Lac2) solution (0 degrees C; below the cloud point of the polymer), followed by rapid heating of the resulting mixture to 50 degrees C, to induce micelle formation ("rapid heating" procedure). Dynamic light scattering (DLS) measurements revealed that approximately 200 nm particles (PDI=0.2) were formed, while transmission electron microscopy (TEM) analysis demonstrated that clusters of SPIONs were present in the core of the micelles. A maximum loading of 40% was obtained, while magnetic resonance imaging (MRI) scanning of the samples demonstrated that the SPION-loaded micelles had high r2 and r2* relaxivities. Furthermore, the r2* values were found to be at least 2-fold higher than the r2 values, confirming the clustering of the SPIONs in the micellar core. The particles showed excellent stability under physiological conditions for 7 days, even in the presence of fetal bovine serum. This, together with their ease of preparation and their size of approximately 200 nm, makes these systems highly suitable for image-guided drug delivery.