On the biodegradability of polyethylene glycol, polypeptoids and poly(2-oxazoline)s

Despite being the gold standard of hydrophilic biomaterials and well known sensitivity of polyethylene glycol (PEG) against oxidative degradation, very little information on the decomposition of PEG under biological oxidative stress can be found in the literature. Poly(2-oxazoline)s (POx) and polypeptoids (POI), two pseudo-polypeptides, have attracted some attention for the use as biomaterials and alternative to PEG with an altered stability against oxidative degradation. All three polymer families are supposedly non-biodegradable, which could be seen as one of their main disadvantages. Here, we present evidence that PEG, POx and POI are degradable by oxidative degradation under biologically relevant conditions. Transition metal catalysed generation of reactive oxygen species (ROS) leads to a pronounced time and concentration dependent degradation of all polymers investigated. While we do not envision oxidative degradation to be of relevance in the short-term usage of these polymers, mid- and long-term biodegradability in vivo appears feasible. Moreover, influence in ROS mediated signalling cascades may be one mechanism how synthetic polymers influence complex cellular processes.