Edaravone-loaded liposomes for retinal protection against oxidative stress-induced retinal damage.

Abstract

To optimize the retinal protective effects of submicron-sized liposomes (ssLips) containing edaravone for intravitreal administration, we investigated the effects of liposomal formulation on the pharmacological effects. Loading of edaravone into ssLips of around 50% entrapment efficiency was achieved by a calcium acetate gradient method. The in vitro radical-scavenging capacity of edaravone-loaded ssLip based on egg phosphatidylcholine (EPC-ssLip) and L-α-distearoyl phosphatidylcholine (DSPC-ssLip) was determined in RGC-5, a neuronal precursor cell line that can be differentiated to resemble retinal ganglion cells. Edaravone-loaded EPC-ssLip scavenged intracellular H(2)O(2) radical more strongly than DSPC-ssLip, although there was only a small difference in cellular uptake of edaravone into RGC-5. An in vivo N-methyl-D-aspartate (NMDA)-induced disease model was used to investigate the retinal protective effects in mice. The edaravone-loaded EPC-ssLip significantly reduced NMDA-induced ganglion cell layer (GCL) cell death compared with free edaravone. Such protective effect was small in the case of DSPC-ssLip. These results may be related to the release profile of the edaravone from ssLips across the inner layers of the retina including GCL, indicating effective retinal protection of EPC-ssLip compared to that of DSPC-ssLip. EPC-ssLip is a promising carrier for edaravone in treating oxidative stress-induced retinal diseases.

• Authors: Kohei Hironaka, Yuta Inokuchi, Takuya Fujisawa, Hiroki Shimazaki, Mai Akane, Yuichi Tozuka, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hideaki Hara, Hirofumi Takeuchi
• Journal: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V (Eur J Pharm Biopharm) Vol. 79 Issue 1 Pg. 119-25 (Sep 2011) ISSN: 1873-3441 [Electronic] Netherlands
• PMID: 21303692 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Excitatory Amino Acid Agonists
• Free Radical Scavengers
• Liposomes
• Phospholipids
• Protective Agents
• N-Methylaspartate
• Edaravone
• Antipyrine

Topics

• Animals
• Antipyrine (analogs & derivatives, chemistry, pharmacology)
• Cell Line
• Drug Compounding
• Drug Delivery Systems
• Edaravone
• Excitatory Amino Acid Agonists (metabolism)
• Eye (metabolism, pathology)
• Free Radical Scavengers (analysis, chemistry)
• Intravitreal Injections
• Liposomes (analysis, chemistry)
• Male
• Mice
• Molecular Targeted Therapy
• N-Methylaspartate (metabolism)
• Oxidative Stress (drug effects, physiology)
• Phospholipids (chemistry, metabolism)
• Protective Agents (chemistry, pharmacology)
• Retina (drug effects, metabolism, pathology)
• Retinal Diseases (chemically induced, drug therapy, metabolism, prevention & control)