Main chain polysulfoxides as active 'stealth' polymers with additional antioxidant and anti-inflammatory behaviour

Farah El Mohtadi, Richard d’Arcy, Xiaoye Yang, Zulfiye Yesim Turhan, Aws Alshamsan, Nicola Tirelli*

*Corresponding author for this work

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Abstract

We present the evaluation of a sulfoxide-based polymer (poly(propylene sulfoxide), PPSO) as a potential ‘stealth’ macromolecule, and at the same time as a pharmacologically active (anti-inflammatory/anti-oxidant) material. The combination of these two concepts may at first seem peculiar since the gold standard polymer in biomaterials and drug delivery, poly(ethylene glycol) (PEG), is ‘stealth’ due to its chemical and biological inertness, which makes it hardly biologically active. Polysulfoxides, on the contrary, may couple a substantial inertness towards biomolecules under homeostatic conditions, with the possibility to scavenge reactive oxygen species (ROS) associated to inflammation. Polysulfoxides, therefore, are rather uniquely, ‘active’ ‘stealth’ polymers. Here, we describe the synthesis of PPSO through controlled oxidation of poly(propylene sulfide) (PPS), which on its turn was obtained via anionic ring-opening polymerization. In vitro, PPSO was characterized by a low toxicity (IC50 ~7 mg/mL at 24 h on human dermal fibroblasts) and a level of complement activation (in human plasma) and macrophage uptake slightly lower than PEG of a similar size. Importantly, and differently from PEG, on LPS-activated macrophages, PPSO showed a strong and dose-dependent ROS (hydrogen peroxide and hypochlorite)-scavenging activity, which resulted in a corresponding reduction of cytokine production.
Original languageEnglish
Article number4583
Number of pages14
JournalInternational Journal of Molecular Sciences
Volume20
Issue number18
DOIs
Publication statusPublished - 17 Sept 2019

Keywords

  • biocompatibility
  • bioinertness
  • oxidants
  • therapeutic polymers
  • responsive polymers
  • polysulfides

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