RESUMO
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.
Assuntos
Antipirina/análogos & derivados , Sistemas de Liberação de Medicamentos , Lipossomos/química , Substâncias Protetoras/química , Retina/patologia , Doenças Retinianas/prevenção & controle , Animais , Antipirina/química , Antipirina/farmacologia , Linhagem Celular , Composição de Medicamentos , Edaravone , Agonistas de Aminoácidos Excitatórios/metabolismo , Olho/metabolismo , Olho/patologia , Sequestradores de Radicais Livres/análise , Sequestradores de Radicais Livres/química , Injeções Intravítreas , Lipossomos/análise , Masculino , Camundongos , Terapia de Alvo Molecular , N-Metilaspartato/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Substâncias Protetoras/farmacologia , Retina/efeitos dos fármacos , Retina/metabolismo , Doenças Retinianas/induzido quimicamente , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/metabolismoRESUMO
In this study, we examined the effect of SUN N8075, a radical scavenger with neuroprotective properties, on murine retinal damage induced by intravitreous injection of N-methyl-d-aspartate (NMDA) or high-intraocular pressure (IOP). In both models, systemic administration of SUN N8075 decreased the cell loss in the ganglion cell layer (GCL) after retinal damage occurred. Moreover, SUN N8075 reduced the number of apoptotic cells and the expression of an oxidative stress marker in GCL in the NMDA model. These findings suggest that SUN N8075 has a neuroprotective effect against retinal damage, presumably via the radical scavenging effect.