Current and forthcoming approaches for systemic detoxification.

Our body must constantly deal with the threat that comes from potentially harmful and poisonous compounds both endogenous and exogenous in nature. Swiss physician Paracelsus (1493–1541) perhaps put it best when he stated that any compound is potentially toxic, as the “dose makes the poison.” These can be drugs, radiochemicals, or peptides/proteins that are introduced into the body either inadvertently (i.e. accidental exposure, infections, or venomous injuries) or deliberately (i.e. suicide attempts or weaponry). Toxic burden can also arise from malfunctioning detoxification mechanisms that result from liver or kidney failure and geneticmetabolic disorders. In total, these harmful substances represent a significant global health issue, and thus technologies for effective detoxification are in high demand. In themajority of cases, the treatments for intoxications remain suboptimal and present significant hurdles that need to be overcome. In the case of pharmaceutical abuse, antidotes only exist for a select few such as acetaminophen, fentanyl, methadone, and alprazolam [1]. Treatments for overdoses are most often supportive (i.e. gastrointestinal decontamination or breathing assistance) and do not directly eliminate or neutralize the causative agents. In the case of animal or insect bites, antivenins can be readilymade, but the need to identify the offending species is a challenge that is further compounded by the poor economics of treating rare afflictions [2]. For enzymatic therapies, some have demonstrated great promise in a laboratory setting, but the fragile nature or suboptimal pharmacokinetic and biodistribution properties of enzymes can significantly hamper their clinical efficacy [3]. It is apparent that there is an unmet medical need for new, more efficient, and versatile detoxification procedures. The number of intoxications has dramatically risen over time—a 2011 data brief from the United States Centers for Disease Control and Prevention indicated that deaths from poisoning had overtaken those from motor vehicle traffic [4]. This is true not only for chemicals and drugs but also for bacterial toxins, as the number of antibiotic-resistant pathogens continues to rise and outpace the development of new treatments. The dire nature of the problem led the President of the United States to issue an executive order in September 2014 for implementing theNational Strategy on Combating Antibiotic-Resistant Bacteria. These troubling trends are not likely to abate in the near future, necessitating the need for accelerated research and development. At first sight, it may appear a bit contradictory to dedicate a special issue of Advanced Drug Delivery Reviews to technologies aimed at removing, rather than delivering, compounds from the body. Upon closer inspection, the commonalities between these two opposing fields becomemore apparent, asmanynew approaches in thefield of detoxification rely on established drug delivery systems, including different forms of nanoparticle technology. The challenges facing the two fields are also oftentimes the same, including the need to improve bioavailability, enhance stability, and modulate localization within the body.