Alginate microgels loaded with temperature sensitive liposomes for magnetic resonance imageable drug release and microgel visualization

The objective of this study was to prepare and characterize alginate microgels loaded with temperature sensitive liposomes, which release their payload after mild hyperthermia. It is further aimed that by using these microgels both the drug release and the microgel deposition can be visualized by magnetic resonance imaging (MRI) after their administration (e.g. in the vicinity of a tumor). To this end, temperature sensitive (TSL) and non-temperature sensitive liposomes (NTSL) loaded with fluorescein (drug mimicking dye) and a T₁ MRI contrast agent (Prohance®, [Gd(HPDO3A)(H₂O)]) were encapsulated in alginate microgels crosslinked by holmium ions (T₂^∗ MRI contrast agent). The drug release could be monitored by the release of [Gd(HPDO3A)(H₂O)] while the microgels could be visualized using MRI via the holmium ions in the microgels. The microgels were prepared with a JetCutter and had an average size of 325 μm and contained ∼0.6 wt% Ho³⁺. Microgels loaded with NTSL (NTSL-Ho-microgels) were stable at 37 and 42°C with only a minimal release of fluorescein and [Gd(HPDO3A)(H₂O)]. Microgels encapsulating TSL (TSL-Ho-microgels) released fluorescein and [Gd(HPDO3A)(H₂O)] only marginally at 37°C while, importantly, their payload was co-released within 2 min at 42°C. TSL-Ho-microgels were administered in an ex vivo sheep kidney via a catheter. Clusters of TSL-Ho-microgels could be visualized via MRI and were deposited in the interlobular blood vessels. In conclusion, these alginate TSL-Ho-microgels are promising systems for real-time, MR-guided embolization and triggered release of drugs in vivo.