Non-fickian diffusion of small-molecule drugs from phase- separated dextran hydrogels through host-guest complexation

Hydrogels have emerged as promising materials for diverse applications in biomedicine and biotechnology, but their use as a drug carrier has been limited by the difficulty of achieving controlled drug release. Herein we report the development of phase-separated dextran hydrogels with 4-arm poly(ethylene glycol)-β-cyclodextrin (4-arm PEG-βCD) microdomains for prolonged release of small-molecule drugs. These hydrogels are designed to enhance the partition of drug molecules in the PEG microdomains through host-guest complexation, leading to delayed drug diffusion through the dextran gel matrix. Three different drugs (β-lapachone, imiquimod and oxaliplatin) were used to investigate the effect of 4-arm PEG-βCD on their partitioning behavior. The mechanical property and microdomain structure of the hydrogels were characterized by oscillatory rheology measurements and confocal laser scanning microscopy, respectively. Interestingly, we observed non-Fickian diffusion phenomena of β-lapachone and imiquimod from the phase-separated hydrogels, suggesting the potential applicability of host-guest interactions for the design of sustained drug release systems.