Cellulose-based injectable hydrogel composite for pH-responsive and controllable drug delivery

Cellulose-based biocompatible, tunable and injectable hydrogels embedded with pH-responsive diblock copolymer micelles were constructed to achieve localized drug delivery with prolonged, stimuli-driven and slow-release function. First, we prepared two types of modified carboxymethyl cellulose (CMC) including hydrazide-modified carboxymethyl cellulose (CMC-NH2) and oxidized carboxymethyl cellulose (CMC - CHO) with varying degrees of oxidation. Then, pH-responsive poly (ethylene oxide)-block-poly (2-(diisopropylamino) ethyl methacrylate) (PEO-b-PDPA) copolymers as micelle cores to carry hydrophobic substances were also synthesized through atom transfer radical polymerization (ATRP). An injectable hydrogel composite system was finally obtained by mixing CMC-NH2 and CMC - CHO polymer suspensions containing PEO-b-PDPA copolymer micelles through a Schiff base reaction. This newly-synthesized, tunable, cellulose-based double barrier system exhibits a pH-triggered, prolonged, and slow-release profile based on the release test using both Nile Red dye and doxorubicin. The hydrogel system also exhibited comparable storage moduli and tunable degradation properties.