Biodegradable polymeric networks (hydrogels) are extensively used for the controlled delivery of pharmaceutical agent to the targeted organs. We employ the stimuli-sensitive spherical hydrogel core coated by a lipid bilayer (lipobeads) as versatile containers for targeted drug delivery and controlled drug release due to their attractive properties of mechanical stability and environmental responsiveness. Particularly, in this work, we focus on the properties of hydrogel core (microgels) degradable in highly reducing environments. Successful performance of lipobeads as the controlled drug delivery systems relies on the degradation behavior of the hydrogel core. This presentation intends to provide the study of the degradation mechanisms of microgels in the presence of reducing agents (dithiothreitol, glutathione) and factors influencing the degradation.<br/>Using the inverse suspension polymerization method, spherical microgels (~Ø10–300 µm) have been synthesized via thermal co-polymerization of acrylamide and acrylonitrile as co-monomers along with <i>N,N'</i>-bis(acryloyl)cystamine as a cross-linker with disulfide bridges. The kinetics of degradation of the fluorescently labeled microgels were studied by confocal microscopy in response to addition of the reductants to show that three steps can be distinguished in the course of degradation: de-cross-linking by breakage of disulfide bridges, polymer network swelling, and outward diffusion of uncleavable polymer chains (erosion). Both the decrease in fluorescence intensity and the increase in microgel size revealed the overall kinetics with the characteristic time (half-life time) which varies from seconds to minutes depending on pH, type and amount of the reductant added, and size of microgels. Thus, fundamental understanding of the microgel degradation phenomena is the important aspect in the design and development of the controlled drug delivery systems including the lipobeadal ones.

Real-time tracking of the degradation and consequent phenomena of biodegradable microgels under presence of reducing agents using confocal microscopy

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