Novel approaches to combat preeclampsia: from new drugs to innovative delivery.

Preeclampsia is a complex disease affecting 2-8% of pregnancies worldwide. It poses significant risk of maternal and perinatal morbidity and mortality. Despite the rising research interest to discover new therapeutic approaches to prevent and treat preeclampsia, options remain limited. Identifying the important pathological stages in the progression of this disease allows us to evaluate effective candidate therapeutics. Three important stages in the pathophysiology are: 1) placental hypoxia and oxidative stress, 2) excess release of anti-angiogenic and pro-inflammatory factors, and 3) widespread systemic endothelial dysfunction and vasoconstriction. Repurposing drugs already safe for use in pregnancy is an attractive option for discovery of novel therapeutics. There are many drugs currently being assessed to treat preeclampsia, including proton pump inhibitors (PPIs), metformin, statins, sulfasalazine, sofalcone, resveratrol, melatonin, and sildenafil citrate. These drugs show positive effects in preclinical studies, targeting placental and endothelial dysfunction. However, using novel therapeutics can raise safety concerns for the developing fetus. Therefore, innovative targeted delivery systems are being developed to safely administer these therapeutics directly to the placenta and/or endothelium. These include nanoparticle delivery systems, developed and used by the oncology field, now being adapted for obstetrics. This technology is currently being assessed in animal models and shows promise for treating preeclampsia. Combining effective therapeutics with targeted drug delivery could be the future of preeclampsia treatment.