Bioreducible hyperbranched polyglycerols with disulfide linkages: Synthesis and biocompatibility evaluation

Abstract

In this article, we describe the development of multifunctional, water-soluble hyperbranched polyglycerols containing redox-sensitive disulfide linkages as a new class of biodegradable polymers. The polymers were synthesized by the anionic ring opening multibranching (co)polymerization of glycidol with an epoxide monomer bearing disulfide groups, 2-((2-oxiran-2-ylmethoxy)ethyl)disulfanyl) ethan-1-ol. Polymerizations were optimized at 65 8C unlike the homopolymerization of glycidol. Both low (5-10 kDa) and high (100 kDa) molecular weight polymers were synthesized in a controlled manner with low polydispersity. The polymers underwent degradation in presence of reducing agents such as tris(2-carboxyethyl)phosphine, dithiothreitol, and glutathione resulting in low molecular weight fragments with thiol groups. Blood compatibility analysis using coagulation, platelet activation, complement activation and red blood cell lysis assays as well as cell toxicity analysis using MTS assay revealed the excellent biocompatibility of these newly synthesized polymer architectures. All these features make these polymers suitable for intracellular delivery of therapeutic molecules.

Hyperbranched Polyols via Copolymerization of 1,2-Butylene Oxide and Glycidol: Comparison of Batch Synthesis and Slow Monomer Addition

“…Glycidol is an established branching comonomer for anionic and cationic multibranching polyether synthesis. ,− Anionic polymerization using slow monomer addition (SMA) gives access to well-defined hyperbranched polyglycerols with a broad range of accessible molecular weights and rather narrow molecular weight distributions. , This technique has been successfully employed for the homopolymerization of glycidol and also for copolymerization with several glycidyl ethers. Via these comonomers, functional groups for “click” coupling reactions, biodegradable cleavage sites, and redox-responsive ferrocene moieties were introduced into the hyperbranched polyether structure in recent years. − …”

Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System

“…We sought the optimal conditions for a gram-scale batch size polymerization at 70 °C with a catalyst that renders reasonable yields, molecular weights above 10 kDa, low polydispersity (Đ), a sufficient degree of branching (DB) and incorporation of intact ester structures of the CL and disulfide bonds of the SSG, respectively. As has been stated by Kizhakkedathu et al before, typical temperatures for the ring-opening polymerization (ROP) of such monomers is around 95 °C; however, the SSG monomer is not stable and disulfide linkages undergo decomposition into thiols and thioethers [ 26 ]. Similar observations were made, and therefore, the polymerization temperature was kept strictly at 70 °C.…”

Core–Shell Copolymers with Brush-on-Hyperbranched Arm Architecture: Synthesis, Dual Thermoresponsive Behaviors, and Nanocarriers

“…Last, we showed that the individual amphiphilic polymers were able to function as nanocarriers to efficiently encapsulate hydrophobic organic dye molecules in aqueous solutions. We hope that the results from this study will not only provide new insights into the understanding of the relationship between molecular structure and thermoresponsive properties, but also enable the future design and production of intelligent polymer materials that can meet the requirements of specialized applications from hyperbranched copolymers. − …”

“…We hope that the results from this study will not only provide new insights into the understanding of the relationship between molecular structure and thermoresponsive properties, but also enable the future design and production of intelligent polymer materials that can meet the requirements of specialized applications from hyperbranched copolymers. 83…”