title: 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.affiliation: Department of Drug Delivery Technology and Science, Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hironaka
authors.forename: Yuta
authors.initials: Y
authors.lastname: Inokuchi
authors.forename: Takuya
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shimazaki
authors.forename: Mai
authors.initials: M
authors.lastname: Akane
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D004339:Drug Compounding; D016503:Drug Delivery Systems; D000077553:Edaravone; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D005123:Eye / Q000378:metabolism / Q000473:pathology; D016166:Free Radical Scavengers / Q000032:analysis / Q000737:chemistry; D058449:Intravitreal Injections; D008081:Liposomes / Q000032:analysis / Q000737:chemistry*; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D016202:N-Methylaspartate / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D020011:Protective Agents / Q000737:chemistry* / Q000494:pharmacology; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012164:Retinal Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D018690:Excitatory Amino Acid Agonists; D016166:Free Radical Scavengers; D008081:Liposomes; D010743:Phospholipids; D020011:Protective Agents; D016202:N-Methylaspartate; D000077553:Edaravone; D000983:Antipyrine