Liposomal 9-Aminoacridine for Treatment of Ischemic Stroke: From Drug Discovery to Drug Delivery.
Nano Lett
; 20(3): 1542-1551, 2020 03 11.
Article
en En
| MEDLINE
| ID: mdl-32039606
ABSTRACT
Neuroinflammation plays a pivotal part in the pathogenesis of stroke. Orphan nuclear receptor NR4A1 is involved in the inflammatory response of microglia and macrophages. In this study, we discovered an old drug, 9-aminoacridine (9-AA), as a novel NR4A1 activator from our in-house FDA-approved drug library, which exhibited anti-inflammatory activities through an NR4A1/IL-10/SOCS3 signaling pathway and modulated the microglia activation. To improve the druggability of 9-AA, different liposomal formulations were screened and investigated. 9-AA-loaded liposome (9-AA/L) was prepared to reduce the adverse effect of 9-AA. Furthermore, 9-AA-loaded PEG/cRGD dual-modified liposome (9-AA/L-PEG-cRGD) was obtained, which displayed prolonged circulation, improved biodistribution, and increased brain accumulation. In the transient middle cerebral artery occlusion (tMCAO) rat model, 9-AA/L-PEG-cRGD significantly reduced brain infarct area, ameliorated ischemic brain injury, and promoted long-term neurological function recovery. This "from drug discovery to drug delivery" methodology provides a potential therapeutic strategy using the liposomal 9-AA, the NR4A1 activator to suppress neuroinflammation for treatment of ischemic stroke.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Descubrimiento de Drogas
/
Aminacrina
/
Accidente Cerebrovascular Isquémico
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Nano Lett
Año:
2020
Tipo del documento:
Article
País de afiliación:
Namibia