Near-infrared activated liposomes for neuroprotection in glaucoma†

Abstract

Neurodegenerative diseases have a profound impact on vision, leading to conditions such as glaucoma, optic neuropathy, and diabetic retinopathy, affecting millions worldwide. These diseases are characterized by the degeneration of retinal ganglion cells (RGCs), resulting in a progressive loss of visual acuity and field, with the threat of irreversible blindness. However, existing treatments, such as eye drops, direct injections, and laser surgeries face significant challenges due to limited efficacy and potential infection. The inefficiency of traditional corneal drug delivery methods is a major obstacle in treating vision neurodegenerative diseases. To address these challenges, we developed a remotely triggered on-demand liposomal delivery system to treat glaucomatous neurodegeneration in mice. We utilized the localized surface plasmon resonance (LSPR) effect of gold nanorods (AuNRs) under near-infrared (NIR) light (808 nm) to control the release of cyclodextrin-encapsulated melatonin from thermally responsive liposomal nanocarriers in the vitreous humor. Due to the transparency of the eye's cornea, NIR light can penetrate deep tissues, enabling on-demand drug delivery to the retina. By enhancing the drug's solubility and stability through cyclodextrin encapsulation, this remotely activated melatonin/HPβCD AuNRs liposomes delivery system can decrease intraocular pressure (IOP) elevation by (24 ± 7)%, enhance the survival rate of RGCs by (77 ± 6)%, and decrease glial fibrillary acidic protein (GFAP) activation by (75 ± 6)% at depth in an acute experimental glaucoma model. This NIR-triggered drug delivery system presents the potential of a promising minimally photo-triggered therapeutic option for glaucoma treatment.