An injectable thermosensitive hydrogel/nanomicelles composite for local chemo-immunotherapy in mouse model of melanoma.

Recently, cancer immunotherapy and its combination with chemotherapy has been considered to improve therapeutic efficacy with lower systemic toxicity. Here, we prepared a thermosensitive hydrogel based hyaluronic acid (HA) encapsulated with macrophage colony-stimulating factor (GM-CSF) and paclitaxel (PTX) for chemoimmunotherapy of cancer. For this purpose, the micelles were prepared with the mixture of pluronic F127 (PF127) and tocopheryl polyethylene glycol (TPGS) and loaded with PTX. In the following step, thermosensitive hydrogel using PF127 and HA was prepared and co-encapsulated with the micelles and GM-CSF. Rheological performance, friability, release patterns for PTX and GM-CSF, and stability of GM-CSF in the hydrogel were evaluated in details.