Gelatin-Based Injectable Hydrogel/Microgel Composite as a Combinational Dual Drug Delivery System for Local Co-delivery of Curcumin and 5-Fluorouracil in Synergistic Therapy of Colorectal Cancer

Chemotherapy using curcumin (Cur) and 5-fluorouracil (5-FU) has been broadly applied to treat colorectal cancer (CRC). In situ chemotherapy mediated by biological macromolecule platforms, such as gelatin-based injectable hydrogels, has recently attracted sizable attention due to their injectability, biocompatibility, and high therapeutic efficacy. Here, a microgel-embedded and micelle-cross-linked injectable hydrogel composite (MMHC) was synthesized for combinational local delivery of 5-FU and curcumin. The hydrophobic core of Pluronic-based micelles in injectable hydrogel was prepared for loading curcumin as a hydrophobic drug. The microgels were physically entrapped into the injectable hydrogel for sustained hydrophilic drug delivery. 5-FU release could be sustained for more than a month from these composite hydrogels, which is considerably longer than that achievable using the microgels alone. The proliferation inhibitory effect and cell cycle arrest were observed in HT-29 cells using the dual drug loaded MMHC system. In conclusion, the Cur/5-FU@MMHC system is a synergistic therapeutic delivery system that can achieve prolonged, sustained-release action for the combination of 5-FU and curcumin against the human colon cancer cell line HT-29.