Protective effects of poly(lactic-co-glycolic acid) nanoparticles loaded with erythropoietin stabilized by sodium cholate against glutamate-induced neurotoxicity.

Abstract

The final aim of this study was to confirm the neuroprotective effects of recombinant human erythropoietin (rhEPO)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles stabilized by sodium cholate (rhEPO-Ch-NP) and compare their effects with those of rhEPO using an in vitro model of cerebral ischemia. Glutamate-induced excitotoxic damage on SH-SY5Y cells, a human neuroblastoma cell line, with or without rhEPO-Ch-NPs was quantitatively evaluated. The rhEPO-Ch-NPs were carefully prepared using a water-in-oil-in-water (w/o/w) emulsion solvent evaporation technique with PLGA, sodium cholate hydrate, and ethyl acetate. The rhEPO-Ch-NPs were fully characterized by both transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). In addition, significant intracellular uptake of these particles was monitored by confocal microscopy. Notably, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and nuclear changes observed by 4',6-diamidino-2-phenylindole (DAPI) staining in SH-SY5Y cells demonstrated that rhEPO-Ch-NPs were safer at any concentration investigated and rescued more neuronal cells, while preserving normocytic features against glutamate-induced excitotoxic damages compared to rhEPO.

• Authors: Ji Heun Jeong, Seung Hee Kang, Jeong Hwan Kim, Kwang Sik Yu, In Ho Lee, Ye Ji Lee, Je Hun Lee, Nam Seob Lee, Young Gil Jeong, Do Kyung Kim, Gyu Hyun Kim, Shin Hye Lee, Seul Ki Hong, Seung-Yun Han, Bo Sun Kang
• Journal: Journal of nanoscience and nanotechnology (J Nanosci Nanotechnol) Vol. 14 Issue 11 Pg. 8365-71 (Nov 2014) ISSN: 1533-4880 [Print] United States
• PMID: 25958529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• Recombinant Proteins
• Erythropoietin
• Polylactic Acid-Polyglycolic Acid Copolymer
• Polyglycolic Acid
• Lactic Acid
• Glutamic Acid
• Sodium Cholate

Topics

• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Stability
• Erythropoietin (chemistry, pharmacology)
• Glutamic Acid (toxicity)
• Humans
• Lactic Acid (chemistry)
• Nanoparticles (chemistry)
• Neuroblastoma
• Neurons (drug effects)
• Neuroprotective Agents (chemistry, pharmacology)
• Particle Size
• Polyglycolic Acid (chemistry)
• Polylactic Acid-Polyglycolic Acid Copolymer
• Recombinant Proteins (chemistry, pharmacology)
• Sodium Cholate (chemistry)