Bilirubin as a Therapeutic Molecule: Challenges and Opportunities

There is strong evidence that serum free bilirubin concentration has significant effects on morbidity and mortality in the most significant health conditions of our times, including cardiovascular disease, diabetes, and obesity/metabolic syndrome. Supplementation of bilirubin in animal and experimental models has reproduced these protective effects, but several factors have slowed the application bilirubin as a therapeutic agent in human patients. Bilirubin is poorly soluble in water, and is a complex molecule that is difficult to synthesize. Current sources of this molecule are animal-derived, creating concerns regarding the risk of virus or prion transmission. However, recent developments in nanoparticle drug delivery, biosynthetic strategies, and drug synthesis have opened new avenues for applying bilirubin as a pharmaceutical agent. This article reviews the chemistry and physiology of bilirubin, potential clinical applications and summarizes current strategies for safe and efficient drug delivery.