Biodegradable Polyglycerols Combining Antioxidant Activity and Sulfation-Induced Complement Inhibition

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Medicinal Chemistry

Background:

• Polyglycerol platforms are valuable for polymer therapeutics due to their inherent multifunctionality and biocompatibility.
• Introducing biodegradability and antioxidant properties enhances polyglycerol's therapeutic potential.
• Cyclic comonomers with thioether and ester functionalities are key to modifying the polyglycerol backbone.

Purpose of the Study:

• To synthesize novel hyperbranched polyglycerol copolymers incorporating biodegradability and antioxidant functionalities.
• To functionalize these copolymers with sulfate groups to explore their potential in modulating inflammatory responses.
• To evaluate the cytocompatibility, antioxidant activity, and complement inhibitory effects of the developed materials.

Main Methods:

• Anionic ring-opening copolymerization of glycidol with 1,4-oxathiepan-7-one (GOTO) or thiodiglycolic anhydride (GTA).
• Characterization of copolymer molecular weight, comonomer incorporation, and water solubility.
• Sulfation of copolymers to yield GOTO-S and GTA-S, followed by assessment of the degree of sulfation.
• Evaluation of cytocompatibility, in vitro antioxidant activity (ABTS assay), and complement activation inhibition.

Main Results:

• Hyperbranched polyglycerol copolymers (GOTO and GTA) with 10 kDa molecular weight and 10 mol% comonomer incorporation were successfully synthesized, maintaining water solubility.
• Sulfated derivatives (GOTO-S and GTA-S) exhibited a high degree of sulfation.
• All synthesized copolymers demonstrated good cytocompatibility and biodegradability under physiological conditions.
• Significant antioxidant activity was observed, attributed to the thioether groups, with GTA showing the strongest radical scavenging capacity.
• Sulfated derivatives effectively inhibited complement activation, with potencies comparable to known anticoagulants like dPGS and heparin.

Conclusions:

• Novel biodegradable and antioxidant polyglycerol copolymers were developed by incorporating cyclic thioether/ester comonomers.
• The sulfated polyglycerol derivatives exhibit potent complement inhibitory activity, suggesting therapeutic potential.
• These materials show promise for applications targeting oxidative stress-related inflammatory conditions.