Recent Advances in Modified Brain-Targeting Drug Delivery Systems for Erythropoietin

Erythropoietin (EPO) is an excellent neuroprotective molecule that decreases the extent of injury caused by various pathologies of the brain, such as Alzheimer's disease, Parkinson's disease, and stroke. However, due to the low permeability of the blood-brain barrier (BBB), a high dose or even an overdose of EPO injections is often administered to achieve a sufficient EPO concentration in the brain. This often leads to many serious adverse reactions. Several studies have presented promising strategies for overcoming the BBB to deliver EPO. These methods include the formation of EPO modified by receptor-mediated transcytosis targeting fusion proteins, cell-penetrating peptides, and nanomaterials. In this review, the clinical progress of modified brain-targeting drug delivery systems of EPO is summarized to provide a scientific basis and new information on the application of EPO in treating diseases of the central nervous system. Here, the production, pharmacological effects, and mechanism of action of the modified EPO, as well as the limiting factors and countermeasures are discussed.