Antioxidant enzymes (AOEs) catalase and superoxide dismutase (SOD) detoxify harmful reactive oxygen species, but the therapeutic utility of AOEs is hindered by inadequate delivery. AOE modification by polyethylene glycol (PEG) and encapsulation in PEG-coated liposomes increases the AOE bioavailability and enhances protective effects in animal models. Pluronic-based micelles formed with AOEs show even more potent protective effects. Furthermore, polymeric nanocarriers (PNCs) based on PEG-copolymers protect encapsulated AOEs from proteolysis and improve delivery to the target cells, such as the endothelium lining the vascular lumen. Antibodies to endothelial determinants conjugated to AOEs or AOE carriers provide targeting and intracellular delivery. Targeted liposomes, protein conjugates and magnetic nanoparticles deliver AOEs to sites of vascular oxidative stress in the cardiovascular, pulmonary and nervous systems. Further advances in nanodevices for AOE delivery will provide a basis for the translation of this approach in the clinical domain.

Oxidative stress is a pathological condition that has been implicated as a central player in a variety of diseases, including vascular and neurodegenerative diseases. More recently, oxidative stress has also been shown to be involved in the biological incompatibility of many materials, especially at the nanoscale. As such, there is a critical need for new biomaterials that can inhibit this response, improving the compatibility of medical devices. In this work, trolox, a synthetic antioxidant and water‐soluble analogue of Vitamin E, is polymerized to form an oxidation active polymer as a new class of biomaterial. Synthesized poly(trolox ester) polymers were formulated into nanoparticles using a single emulsion technique, and their size was controlled by changing the polymer concentration in the organic solvent. Nanoparticle cytotoxicity, protective effects against cellular oxidative stress, and degradation kinetics were all evaluated. Poly(trolox ester) nanoparticles were found to have little to no cytotoxicity and were capable of suppressing cellular oxidative stress induced by cobalt nanoparticles. In vitro degradation studies of poly(trolox ester) nanoparticles indicate that the antioxidant activity of nanoparticles was derived from its enzymatic degradation to release active antioxidants.

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In a variety of biomedical applications (e.g., tissue engineering, drug delivery, etc.), the role of a bioactive material is to serve as a platform by which one can modulate the cellular response into a desired role. Of the methods by which one may achieve this control (e.g., shape, structure, binding, growth factor release), the control of the cellular redox state has been under evaluated. Ideally, the ability to tune the redox state of a cell provides an additional level of control over a variety of cellular responses including, cell differentiation, proliferation, and apoptosis. Yet, in order to achieve such control, it is important to know both the overall oxidative status of the cell and what molecular targets are being oxidized. In this work, poly (trolox ester) nanoparticles were evaluated for their ability to either inhibit or induce cellular oxidative stress in a dose-dependent fashion. This polymer delivery form possessed a unique ability to suppress protein oxidation, a feature not seen in the free drug form, emphasizing the advantage of the delivery/dosage formulation has upon regulating cellular response.