Biodegradable Polyglycerols Combining Antioxidant Activity and Sulfation-Induced Complement Inhibition

Polyglycerol platforms are promising for polymer therapeutics due to their multifunctionality and biocompatibility. Our aim was to introduce biodegradability as well as antioxidant properties to the polyglycerol backbone using cyclic comonomers with thioether and ester functionalities. Anionic ring-opening copolymerization of glycidol and either 1,4-oxathiepan-7-one or thiodiglycolic anhydride yielded the hyperbranched structures: GOTO or GTA, respectively. Characterization confirmed molecular weights of 10 kDa and the successful incorporation of 10 mol % comonomer while maintaining water solubility. Sulfated derivatives, GOTO-S and GTA-S, were obtained with a high degree of sulfation. All copolymers showed good cytocompatibility as well as degradability under physiological conditions. Significant antioxidant activity attributed to the thioether groups of the copolymers was demonstrated via the ABTS radical scavenging assay. GTA emerged as the strongest radical scavenger among the polymers tested, likewise, GTA-S outperformed GOTO-S. Notably, the sulfated derivatives effectively inhibit complement activation with potencies comparable to dPGS and heparin, demonstrating their potential for applications in oxidative stress-related inflammation.