Stimuli-responsive hydrogels - Drugs take control

Wilfried Weber and colleagues discuss an ingenious new route to trigger drug release that involves a widely used and well-tolerated drug to liberate another drug from a matrix. The system is a hydrogel composed of a polymer with a proportion of side- chains linked to the protein bacterial gyrase sub-unit B (GyrB). This protein is the normal target for antibiotics from the aminocoumarin family and thus GyrB binds strongly to these compounds. Weber uses a highly potent biotherapeutic, human vascular endothelial growth factor (VEGF). He prepared a mutant version of VEGF with a hexa-hitstidine sequence to enable it to bind in nickel nitrilotriacetic acid groups attached to the polymer backbone. The released protein is strongly active and is able to stimulate the proliferation of a relevant cell line, primary human umbilical vein endothelial cells, over at least a 96-hr period. The approach is powerful because it uses relatively simple trigger compounds at concentrations that are achievable in the clinic.