Redox-Degradable Biocompatible Hyperbranched Polyglycerols: Synthesis, Copolymerization Kinetics, Degradation, and Biocompatibility

Polymers that are biocompatible and degrade in response to stimuli are highly desirable as smart drug-delivery carriers. We report the first novel redox-degradable hyperbranched polyglycerols. A glycerol monomer containing a disulfide bond, i.e., 2-((2-(oxiran-2-ylmethoxy)­ethyl)­disulfanyl)­ethan-1-ol (SSG), was designed and polymerized through anionic ring-opening multibranching polymerization to yield a series of redox-degradable hyperbranched polyglycerols (PSSGs) with controlled molecular weights (2000–11 000 g/mol) and relatively low molecular weight distributions (<i>M</i>_w/<i>M</i>_n < 1.15). In addition, copolymerization with a nondegradable glycerol (G) monomer provided P­(G-<i>co</i>-SSG) copolymers, which contained an adjustable fraction of degradable moieties within their polyglycerol backbones. The polymerization was characterized using ¹H and ¹³C NMR spectroscopy, GPC, and MALDI-ToF mass spectrometry. The copolymerization process was also evaluated using quantitative <i>in situ</i> ¹³C NMR kinetic measurements in bulk, which revealed that the reaction kinetics of G were faster than those of the SSG monomer, leading to a gradient during the copolymerization process. Furthermore, we explored the redox-responsive degradation of the polymers upon treatment with a reducing agent, which resulted in selective degradation of the polymers in small segments. <i>In vitro</i> cytotoxicity studies, such as MTT and CCK-8 assays, revealed the superior biocompatibility of these new polymers even at high concentrations of 500 μg/mL. We anticipate that these novel redox-degradable and highly biocompatible polyglycerols will find applications in a variety of emerging biomedical fields