“Dumb” pH-Independent and Biocompatible Hydrogels Formed by Copolymers of Long-Chain Alkyl Glycidyl Ethers and Ethylene Oxide

Abstract

The formation and rheological properties of hydrogels based on amphiphilic ABA triblock polyether copolymers are described, relying solely on the hydrophobic interaction of long-chain alkyl glycidyl ether (AlkGE)- based A-blocks that are combined with a hydrophilic poly­(ethylene glycol) (PEG) midblock. Via anionic ring-opening copolymerization (AROP), ethylene oxide (EO) and long-chain alkyl glycidyl ethers (AlkGEs) were copolymerized, using deprotonated poly­(ethylene glycol) (PEG) macroinitiators (M n of 10, 20 kg mol–1). The polymerization afforded amphiphilic ABA triblock copolymers with molar masses in the range of 21–32 kg mol–1 and dispersities (Đ) of Đ = 1.07–1.17. Kinetic studies revealed random copolymerization of EO and AlkGE, indicating random spacing of the hydrophobic AlkGE units by polar EO units. Following this approach, the hydrophobicity of the apolar blocks of amphiphilic ABA triblock polyethers can be tailored. Detailed rheological measurements confirmed the successful formation of hydrogels at different pH values as a consequence of nonpolar interactions and alkyl chain crystallization. Hydrogel formation was also observed at different ionic strengths (i.e., varied salt concentration), based on the hydrophobic aggregates. This behavior is in contrast to other often-used supramolecular cross-linking strategies, such as Coulomb interactions, complexation, or hydrogen bonding. Micro-differential scanning calorimetry (μ-DSC) measurements of the hydrogels revealed crystalline hydrophobic domains with melting temperatures in the physiological temperature range. In 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assays, diblock copolymers possessing structural analogy to the triblock copolymers were studied to assess the general cytotoxicity of amphiphilic polyethers bearing long alkyl chains at the polyether backbone, using splenic immune cells. At intermediate polymer concentrations, no cytotoxic effects were observed. This indicates that long-chain alkyl glycidyl ethers are promising for the introduction of highly hydrophobic as well as crystalline motifs at the polyether backbone in hydrogels for biomedical purposes.

Unexpected Random Copolymerization of Propylene Oxide with Glycidyl Methyl Ether via Double Metal Cyanide Catalysis: Introducing Polarity in Polypropylene Oxide

“…The current observation also differs from the AROP of PO and GME, which likewise results in a gradient structure ( r PO = 0.305 and r GME = 3.15) . Altogether, with regard to monomer reactivity, the presented copolymerization of PO and GME via DMC catalysis seems to be comparable to known copolymerizations of EO and various glycidyl ethers − rather than the commonly observed high reactivity of PO in DMC catalysis.…”

Micelle and Nanotape Formation of Benzene Tricarboxamide Analogues with Selective Cancer Cell Cytotoxicity

“…Although unmodified PEG itself is considered relatively benign to cells, , and indeed is incorporated in certain therapeutics to provide enhanced stability and longer circulation in vivo, PEG derivatives can show cytotoxicity . The activity of the BTA analogues in terms of selective cytotoxicity against cancer cells was investigated using assays comparing the viabilities of L929 fibroblasts and MCF-7 breast cancer cells.…”

In Situ Kinetics Reveal the Influence of Solvents and Monomer Structure on the Anionic Ring‐Opening Copolymerization of Epoxides

“…Consequently, non‐terminal models, for example, the Jaacks method [ 29 ] can be employed to investigate the underlying copolymerization kinetics in AROP. [ 28,23,17 ]…”