Enhanced Pulsatile Drug Release from Injectable Magnetic Hydrogels with Embedded Thermosensitive Microgels

Nanocomposite in situ-gelling hydrogels containing both superparamagnetic iron oxide nanoparticles (SPIONs) and thermoresponsive microgels are demonstrated to facilitate pulsatile, high-low release of a model drug (4 kDa fluorescein labeled dextran). The materials can be injected through a minimally invasive route, facilitate a similar to 4-fold enhancement of release when pulsed on relative to the off state, and, in contrast to previous gel-based systems, can maintain pulsatile release properties over multiple cycles and multiple days instead of only hours. Optimal pulsatile release is achieved when the microgel transition temperature is engineered to lie just above the (physiological) incubation temperature. Coupled with the demonstrated degradability of the nanocomposites and the cytocompatibility of all nanocomposite components, we anticipate these nanocomposites have potential to facilitate physiologically relevant, controlled pulsatile drug delivery.