Degradation Kinetics of Disulfide Cross-Linked Microgels: Real-Time Monitoring by Confocal Microscopy

Although biodegradable microgels represent a useful drug delivery system, questions remain regarding the kinetics of gel degradation and subsequent drug release. Spherical microgels (similar to circle divide 10-300 mu m) were synthesized using an inverse suspension polymerization method. Specifically, acrylamide and acrylonitrile monomers were thermally co-polymerized with N,N'-bis(acryloyl)cystamine as a cross-linker with disulfide bridges. The kinetics and mechanism of degradation of these cross-linked, degradable, fluorescently labeled microgels (PAAm-AN-BAC-FA) were quantitatively studied under confocal microscopy at various concentrations of glutathione (reducing agent) ranging from 0.06 to 91.8 mM. It was found that polymer network degradation via the cleavage of disulfide bonds was accompanied by two overlapping processes: diffusion-driven swelling and dissolution-driven erosion. A slow increase in microgel size (swelling) resulted from partial de-cross-linking in the bulk of the microgel, whereas a faster decrease in fluorescence intensity (erosion) resulted from the complete cleavage of disulfide bonds and the release of uncleaved polymeric chains from the microgel immediate surface into the solution. Swelling and erosion exhibited distinct kinetics and characteristic times. Importantly, the dependence of kinetics on glutathione concentration for both swelling and erosion suggests that degradation would occur faster in cancer cells (higher concentration of reductants) than in normal cells (lower concentration of reductants), such that drug release profiles would be correspondingly different. A greater comprehension of microgel degradation kinetics would help in (i) predicting the drug release profiles for novel multifunctional drug delivery systems and (ii) using redox-sensitive degradable hydrogel particles to determine the concentrations of reducing agents either in vitro or in vivo.

Automated summary

This study investigates the kinetics of degradation and drug release of biodegradable microgels. The results show that degradation occurs through the cleavage of disulfide bonds, leading to swelling and erosion processes. The kinetics of swelling and erosion are dependent on the concentration of the reducing agent glutathione. These findings suggest that drug release profiles can be different in cancer cells compared to normal cells.