‘Capsosomes’ To Treat Phenylketonuria

Replacing defective enzymes is a promising treatment for many diseases, but in practice it is difficult to achieve because enzymes are readily degraded in the digestive tract or bloodstream. Encasing enzymes in liposomes that are layered on a silica particle and then coated with a polymer to create a “capsosome” is a new approach that could help with the delivery, reports a group led by Leticia Hosta-Rigau and Brigitte Städler of Denmark’s Aarhus University (Adv. Funct. Mater. 2015, DOI: 10.1002/adfm.201404180). The researchers think the technology could be used for controlling phenylketonuria, a condition involving a genetic defect that disables a liver enzyme that metabolizes phenylalanine into tyrosine. The consequent buildup of phenylalanine causes brain damage, and the only treatment is dietary control to limit phenylalanine consumption. Hosta-Rigau, Städler, and colleagues loaded their capsosomes with phenylalanine ammonia lyase, an enzyme that converts phenylalanine to nontoxic trans-cinnamic acid. They tested the delivery system in microfluidic devices that allowed them to simulate flow over human intestinal cells. The capsosomes successfully converted phenylalanine to trans-cinnamic acid while staying outside the cells and showing no sign of cytotoxicity.