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Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 2468457, 23 pages
https://doi.org/10.1155/2018/2468457
Review Article

Insights on Localized and Systemic Delivery of Redox-Based Therapeutics

1Department of Surgery, Division of Vascular Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
4Division of Pharmacoengineering and Molecular Pharmaceutics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
5Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA

Correspondence should be addressed to Edward S. M. Bahnson; ude.cnu.dem@nosnhab_drawde

Received 30 October 2017; Accepted 18 December 2017; Published 14 February 2018

Academic Editor: Maria C. Franco

Copyright © 2018 Nicholas E. Buglak et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Reactive oxygen and nitrogen species are indispensable in cellular physiology and signaling. Overproduction of these reactive species or failure to maintain their levels within the physiological range results in cellular redox dysfunction, often termed cellular oxidative stress. Redox dysfunction in turn is at the molecular basis of disease etiology and progression. Accordingly, antioxidant intervention to restore redox homeostasis has been pursued as a therapeutic strategy for cardiovascular disease, cancer, and neurodegenerative disorders among many others. Despite preliminary success in cellular and animal models, redox-based interventions have virtually been ineffective in clinical trials. We propose the fundamental reason for their failure is a flawed delivery approach. Namely, systemic delivery for a geographically local disease limits the effectiveness of the antioxidant. We take a critical look at the literature and evaluate successful and unsuccessful approaches to translation of redox intervention to the clinical arena, including dose, patient selection, and delivery approach. We argue that when interpreting a failed antioxidant-based clinical trial, it is crucial to take into account these variables and importantly, whether the drug had an effect on the redox status. Finally, we propose that local and targeted delivery hold promise to translate redox-based therapies from the bench to the bedside.