A Dual-Drug Nanohybrid System Incorporating Nimodipine and Brain-Derived Neurotrophic Factor Promotes Retinal Ganglion Cells Survival

ADVANCED THERAPEUTICS(2023)

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摘要
Glaucoma, a leading cause of irreversible visual impairments and even blindness, is characterized by elevated intraocular pressure and progressive loss of structure and function of neuronal systems. To effectively protect neuronal systems from damage caused by elevated intraocular pressure, a novel dual-drug nanohybrid has been developed by incorporating brain-derived neurotrophic factor (BDNF)-loaded mesoporous silica nanoparticles (BDNF@MSN) into the thermogel matrix with nimodipine (NMD) (BDNF@MSN-NMD@Thermogel). The carrier materials (i.e., silica and thermogel) in this nanohybrid do not show any cytotoxicity to human lens epithelial cells and rat retinal precursor cells. This nanohybrid regulates the in vitro release of BDNF and NMD in a sustainable way for weeks. In optic nerve crush rodent models, a single intravitreal injection of BDNF@MSN-NMD@Thermogel inhibits retinal neuroinflammation, significantly promotes retinal ganglion cells survival and restores visual function for nearly three months. This nanohybrid is thus a promising alternative for effective neuroprotection treatment for neuroinflammation-related neurodegenerative diseases.
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关键词
brain-derived neurotrophic factor (BDNF),dual-drug nanohybrid,nimodipine,retinal ganglion cells (RGCs),synergistic treatment,visual function
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