Rapidly in situ forming polyphosphoester-based hydrogels for injectable drug delivery carriers

In situ forming hydrogels allow the modulation of physicochemical properties and are providing new opportunities for biomedical applications. Here, the preparation and characterization of a series of rapidly in situ forming and pH-responsive hydrogels with different crosslinking degrees are reported, which were achieved by accelerated free radical copolymerization of polyphosphoester-based macrocrosslinker and 2-(dimethylamino)ethyl methacrylate (DMAEMA) monomer. The hydrogel formation can be completed very quickly under mild conditions, ranging from several to tens of minutes with varying concentrations of components. The polyphosphoester-based macrocrosslinker was synthesized via a combination of ring-opening polymerization and post-polymerization modification, and it was characterized by H-1 NMR, P-31 NMR, and GPC measurements. The sol-gel transition was monitored by dynamic time sweep rheological analysis. Moreover, the swelling kinetics, interior morphology, pH-responsive property, in vitro cytotoxicity and drug release of these hydrogels were characterized. The results indicate that these hydrogels show great potential as injectable drug delivery system.