Injectable shell-crosslinked F127 micelle/hydrogel composites with pH and redox sensitivity for combined release of anticancer drugs

• A novel dual drug carrier is constructed by injectable micelle/hydrogel composite.
• This drug carrier has redox-sensitivity and pH-sensitivity.
• The preparation is inexpensive, facile and fast.
• The system can load and deliver hydrophobic and hydrophilic drugs simultaneously.
• The system can be used in combination chemotherapy for cancer treatment.

Combination chemotherapy as a preferred strategy for cancer treatment has been widely developed recently. However, single drug carriers of the combination chemotherapy systems are difficult to address the performance requirement that delivers hydrophilic and hydrophobic drugs simultaneously. In this work, a smart dual drug delivery system of injectable micelle/hydrogel composite was developed. This smart drug delivery system consists of curcumin (Cur) loaded shell-crosslinked F127 micelle and 5-fluorouracil (Fu) dispersed chitosan/oxidized dextran (CS/ODex) hydrogel. Both of the shell-crosslinked F127 micelle and CS/ODex hydrogel were prepared based on Schiff base bonds, which provides pH-sensitivity and biodegradability for the system. In addition, disulfide bonds were introduced in the shell of F127 micelle, allowing for redox-sensitivity of the system. The system was detailed characterized by 1H NMR, FTIR, TEM, SEM, DLS and fluorescence spectroscopy. Independent release behaviors of the two drugs are observed under conditions of different precursor concentration, different CS/ODex proportion, different pH and different concentration of DTT. The results show that the drug carrier has pH and redox sensitivity and the release rate can be adjusted by the concentration of the precursor solution. In vitro degradation experiment and cytotoxicity assay determine that the system has good biodegradability and biocompatibility. These results indicated that the injectable shell-crosslinked F127 micelle/hydrogel composite may load and deliver hydrophobic and hydrophilic drugs simultaneously and find application in combination chemotherapy for cancer treatment.