Hooked on Cryogels: A Carbamate Linker Based Depot for Slow Drug Release

Poly(ethylene glycol) (PEG) based bulk hydrogels and cryogels containing activated carbonate groups as amine reactive handles to facilitate drug conjugations through carbamate linkages were fabricated and evaluated as slow releasing drug reservoirs. As an initial approach, photopolymerization of N-hydroxysuccinimide (NHS)-activated carbonate functional group containing monomer and PEG-methacrylate in the presence of a cross-linker was utilized to obtain bulk hydrogels with high gel conversions. The resultant hydrogels possessed moderate water uptake (170-340%) which was dependent on the monomer ratios. These hydrogels were functionalized with an anticancer drug, namely, doxorubicin. Surprisingly, while negligible drug release was observed from the bulk hydrogels under normal pH, only about 6% drug release was observed under acidic condition. Limited swelling of these hydrogels as well as lack of porous structure as deduced from scanning electron microscopy analysis might explain the poor drug release. To enhance the drug releasing capacity of these hydrogels that might stem from the increased porosity, reactive carbonate group bearing cryogels were synthesized. Compared to the bulk hydrogels, cryogels were highly porous in structure and also possessed much higher swelling capacity (1150-1500%). As a result of these distinctions, a 7-fold enhancement in drug release was observed for the cryogel system compared to the relating hydrogel. In vitro studies demonstrated that the anticancer drug doxorubicin conjugated through carbamate linkers to the cryogels was released and proved effective against MDA-MB-231 human breast cancer cells. Overall, a novel class of slow releasing nontoxic hydrogel and cryogel scaffolds with potential applications as anticancer drug reservoirs was realized.