Fishing for fire: strategies for biological targeting and criteria for material design in anti-inflammatory therapies

Inflammatory pathologies are a growing burden for developed societies, and the tools offered by medicinal chemistry/biotechnology have provided us with an armamentarium of active principles. Unfortunately, most of them are marred by very significant side effects that can be summarized by two words: poor targeting (of cells, of tissues, etc.). This review provides a broad overview of the approaches and of the materials used to obtain an inflammation-responsive or inflammation-targeted behavior, which can be used to improve anti-inflammatory therapies. Here, we first define the biochemical factors that may allow both to recognize and to target an inflamed environment, for example, the leakiness of capillaries, the presence of oxidants (reactive oxygen species), or of upregulated receptors/enzymes. We then review the systems that have shown the possibility to accumulate in inflamed tissues, respond to its stimuli, or bind to activated inflammatory cells, separately discussing payload/carrier (guest/host) systems and macromolecular prodrugs/conjugates. Copyright (c) 2014 John Wiley & Sons, Ltd.