Local co-delivery of 5-fluorouracil and curcumin using Schiff's base cross-linked injectable hydrogels for colorectal cancer combination therapy

Abstract 5-Fluorouracil (5-FU) in combination with curcumin has been widely investigated for colon carcinoma cancer. The combination therapy using drug delivery systems will hopefully result in improved therapeutic efficacy, targeted delivery and controlled release of therapeutic agents. However, development of single drug carriers for simultaneous administration of both hydrophobic (curcumin) and hydrophilic (5-FU) drugs is still challenging. Here, the micelle-crosslinked hydrogel was synthesized through a reversible Schiff’s based reaction between gelatin-hydrazide (Gel-ADH) and self-assembled Pluronic F127-benzaldehyde (PF127-CHO) micelles. The 5-FU was incorporated in hydrogel network and curcumin was incorporated in core of micelles embedded in hydrogel. The in vitro drugs release profile in pH 6.8 and 7.4 exhibited a pH-responsive release pattern and showed more sustain release of 5-FU in combination with curcumin. The exposure of the combined drug formulation in colon cancer cells (HT-29) proved the enhanced anticancer effects. The synergistic inhibitory effects on the cell cycle progression and cell proliferation in HT-29 cells were also confirmed. The developed hydrogel showed the more efficacy for the simultaneous administration of two drugs with different hydrophilicity.