Sustained Release of Neuroprotective Drugs Curcumin and Edaravone from Supramolecular Hydrogel for Ischemic Stroke Treatment

Ischemic stroke is a major cause of death and disability worldwide. The poor drug delivery to cerebral ischemic regions remains a challenging issue for ischemic stroke treatment. Curcumin (Cur) and edaravone (EDV) show remarkable therapeutic effects on ischemic stroke. However, the short half-life and poor aqueous solubility limit their application for long-term and effective neuroprotection. Cur and EDV with a well-studied hydrogelator Nap-Phe-Phe-Tyr-OH (NapFFY) is co-assembled to prepare a novel supramolecular peptide hydrogel EDV/Cur/NapFFY, which can improve their bioavailability and transport the hydrophobic drugs to ischemic sites precisely by local administration. In vitro release test demonstrate that co-assembly with NapFFY enables continuous release of Cur and EDV for about two weeks. Animal studies found that EDV/Cur/NapFFY hydrogel can effectively promote brain plasticity and enhance the functional recovery on the photothrombotic mouse model. Overall, the work reveales the great application potential of supramolecular peptide hydrogel delivery system EDV/Cur/NapFFY in promoting repair and recovery of ischemic stroke.