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

被引：60

作者：

Hironaka, Kohei ^{[1
]}

Inokuchi, Yuta ^{[2
]}

Fujisawa, Takuya ^{[1
]}

Shimazaki, Hiroki ^{[2
]}

Akane, Mai ^{[2
]}

Tozuka, Yuichi ^{[1
]}

Tsuruma, Kazuhiro ^{[2
]}

Shimazawa, Masamitsu ^{[2
]}

Hara, Hideaki ^{[2
]}

Takeuchi, Hirofumi ^{[1
]}

机构：

[1] Gifu Pharmaceut Univ, Dept Drug Delivery Technol & Sci, Gifu 5011196, Japan

[2] Gifu Pharmaceut Univ, Dept Biofunct Evaluat, Gifu 5011196, Japan

来源：

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2011年 / 79卷 / 01期

关键词：

Edaravone; Liposome; Calcium acetate gradient method; Intravitreal injection; Retina; Oxidative stress; FREE-RADICAL SCAVENGER; LIPID-COMPOSITION; IN-VITRO; INTRAVITREAL; PHARMACOKINETICS; NANOPARTICLES; GLUTAMATE;

D O I：

10.1016/j.ejpb.2011.01.019

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

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-alpha-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 H2O2 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. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：119 / 125

页数：7

共 30 条

[1]

PREPARATION, CHARACTERIZATION, AND IN VIVO EVALUATION OF NANOLIPOSOMES-ENCAPSULATED BEVACIZUMAB (AVASTIN) FOR INTRAVITREAL ADMINISTRATION [J].