载有依达拉奉的脂质体，用于保护视网膜免受氧化应激诱导的视网膜损伤。

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

机构信息

Department of Drug Delivery Technology and Science, Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu, Japan.

出版信息

Eur J Pharm Biopharm. 2011 Sep;79(1):119-25. doi: 10.1016/j.ejpb.2011.01.019. Epub 2011 Feb 15.

DOI:10.1016/j.ejpb.2011.01.019

PMID:21303692

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.

摘要

为了优化含有依达拉奉的亚微米级脂质体（ssLip）经玻璃体内给药的视网膜保护作用，我们研究了脂质体制剂对药效的影响。通过醋酸钙梯度法，将依达拉奉载入包封率约为 50%的 ssLip 中。以可分化为类似视网膜神经节细胞的神经前体细胞系 RGC-5 为模型，测定了载有依达拉奉的基于卵磷酯（EPC-ssLip）和 L-α-二硬脂酰磷脂酰胆碱（DSPC-ssLip）的 ssLip 的体外清除自由基能力。尽管依达拉奉进入 RGC-5 的细胞摄取量仅有微小差异，但载有依达拉奉的 EPC-ssLip 比 DSPC-ssLip 更能强烈地清除细胞内的 H 2 O 2 自由基。采用体内 N-甲基-D-天冬氨酸（NMDA）诱导疾病模型，研究了在小鼠中的视网膜保护作用。与游离依达拉奉相比，载有依达拉奉的 EPC-ssLip 显著降低了 NMDA 诱导的神经节细胞层（GCL）细胞死亡。而 DSPC-ssLip 的保护作用较小。这些结果可能与 ssLip 中依达拉奉在内层视网膜（包括 GCL）中的释放模式有关，表明 EPC-ssLip 比 DSPC-ssLip 具有更有效的视网膜保护作用。EPC-ssLip 是治疗氧化应激诱导的视网膜疾病的依达拉奉的一种有前途的载体。