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 complete 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) in responding to near-infrared (NIR) light to control the release of cyclodextrin-encapsulated melatonin from thermally responsive liposomal nanocarriers in vitreous humor. Due to the transparency of eye corneal, NIR light can penetrate deep tissues, enabling on-demand drug delivery to the retina. With the drug's solubility and stability enhanced by cyclodextrin encapsulation, this remotely activated 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) % in depth in an acute experimental glaucoma model. This approach offers a non-invasive, site-specific, and efficient drug delivery method, potentially advancing vision disease therapy.