Targeting vascular inflammation through emerging methods and drug carriers

Acute inflammation is a common dangerous component of pathogenesis of many prevalent conditions with high morbidity and mortality including sepsis, thrombosis, acute respiratory distress syndrome (ARDS), COVID-19, myocardial and cerebral ischemia-reperfusion, infection, and trauma. Inflammatory changes of the vasculature and blood mediate the course and outcome of the pathology in the tissue site of insult, remote organs and systemically. Endothelial cells lining the luminal surface of the vasculature play the key regulatory functions in the body, distinct under normal vs. pathological conditions. In theory, pharmacological interventions in the endothelial cells might enable therapeutic correction of the overzealous damaging pro-inflammatory and pro-thrombotic changes in the vasculature. However, current agents and drug delivery systems (DDS) have inadequate pharmacokinetics and lack the spatiotemporal precision of vascular delivery in the context of acute inflammation. To attain this level of precision, many groups design DDS targeted to specific endothelial surface determinants. These DDS are able to provide specificity for desired tissues, organs, cells, and sub-cellular compartments needed for a particular intervention. We provide a brief overview of endothelial determinants, design of DDS targeted to these molecules, their performance in experimental models with focus on animal studies and appraisal of emerging new approaches. Particular attention is paid to challenges and perspectives of targeted therapeutics and nanomedicine for advanced management of acute inflammation.