Improvement of memory deficits in the rat model of Alzheimer's disease by erythropoietin-loaded solid lipid nanoparticles

Abstract Erythropoietin (EPO), a hematopoietic factor, is one of the promising neuroprotective candidates in neurodegenerative disorders such as Alzheimer's disease (AD). Due to the high molecular weight, hydrophilicity and rapid clearance from circulation, EPO could not completely pass the blood-brain barrier in the case of systemic administration. To overcome this limitation, EPO-loaded Solid Lipid Nanoparticle (EPO-SLN) was developed in this study using a double emulsion solvent evaporation method (W1/O/W2). Glycerin monostearate (GMS), span®80/span®60, Dichloromethane (DCM) and tween®80 were chosen as lipid, internal phase surfactants, solvent, and external aqueous phase surfactant, respectively. After physicochemical evaluations, the effect of EPO-SLN on the beta-amyloid-induced AD-like animal model was investigated. In vivo evaluations, it was demonstrated that the memory was significantly restored in cognitive deficit rats treated with EPO-SLN compared to the rats treated with native drug using the Morris water maze test. In addition, EPO-SLN reduced the oxidative stress, ADP/ATP ratio, and beta-amyloid plaque deposition in the hippocampus more effectively than the free EPO. Hence, the designed SLN can be regarded as a promising system for safe and effective delivery of EPO in the AD.