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.
Highlights
Poly(ethylene glycol) (PEG) has been considered the golden standard of synthetic macromolecules in biomedical applications, be it in the preparation of carriers for drug delivery, proteins with reduced immunogenicity, [3,4], or matrices for tissue engineering/regenerative medicine [5]
We have focused on polysulfides, employing them as reactive oxygen species (ROS)-scavengers, and as a result as anti-inflammatory agents [43,44]
The anionic ring-opening polymerization (ROP) of propylene sulfide (PS) was initiated by a thiolate generated in situ through the deprotection of a thioacetate, in the presence of the reducing agent, tributylphosphine (Figure 1A); this combination minimizes the presence of disulfides, which act as chain transfer agents in episulfide polymerization [46], preventing them from compromising the identity of the terminal groups of the final polymers, which would in turn increase their molecular weight dispersity
Summary
Poly(ethylene glycol) (PEG) has been considered the golden standard of synthetic macromolecules in biomedical applications, be it in the preparation of carriers for drug delivery (including several marketed or FDA-approved products [1,2]), proteins with reduced immunogenicity, [3,4], or matrices for tissue engineering/regenerative medicine [5].
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