A sequential delivery system employing the synergism of EPO and NGF promotes sciatic nerve repair

The different mechanisms of nerve growth factor (NGF) and erythropoietin (EPO) in promoting repair of peripheral nerve injuries suggest a potential therapeutic application through the synergism of the two. Yet NGF has also been reported to induce early nerve apoptosis after injury. To utilize the potential synergism of NGF and EPO while minimize the possible defect, in this study, we first confirmed the time dependency of NGF caused nerve apoptosis, and then established a sequential and sustained delivery system for NGF and EPO with poly(lactide-co-glycolide) (PLGA), which has been approved by the US FDA for human use because of its injectable, biocompatible, and biodegradable properties. EPO was encapsulated in PLGA-microspheres (MS) for sustained releasing, while NGF was encapsulated in BSA-incorporated PLGA (B-PLGA) MS to postpone its release. In rat model of sciatic nerve injury, co-delivery of EPO/PLGA-MS and NGF/B-PLGA-MS resulted in significant nerve recovery. Hopefully, this sequential delivery system could provide a new therapeutic strategy for peripheral never injury.