NeuProIO: A dual-action solid drug nanoparticle topical formulation for simultaneous intraocular pressure reduction and neuroprotection for glaucoma

Abstract: Glaucoma is a leading cause of irreversible blindness, primarily due to elevated intraocular pressure (IOP) that damages the retina and optic nerve. Most topical glaucoma treatments focus solely on IOP-lowering without direct neuroprotection, as drug delivery to the posterior eye is challenging. Here, we developed NeuProIO, a dual-action solid drug nanoparticle (NP) eye drop for simultaneous IOP reduction and neuroprotection. Using flash nanoprecipitation in a multi-inlet vortex mixer, we fabricated the first NeuProIO solid drug NPs incorporating the repurposed neuroprotective agent maprotiline (MAP) and the IOP-lowering agent betaxolol (BX), forming MAP/BX NPs for synergistic glaucoma treatment. The NeuProIO improved stability and ocular biocompatibility versus conventional eye drops and markedly enhanced ocular penetration. The IOP-lowering effect was evaluated using normotensive rats. Single topical dosing sustained an effective IOP control (> 15% IOP reduction) for 72 h and multiple topical dosing (once every 2 days, 3 doses in total) maintained a lower IOP for 10 days, suggesting the potential for reduced dose frequency. Beyond its IOP-lowering effect, BX significantly enhanced the posterior segment delivery of MAP in MAP/BX NPs, resulting in retinal and optic nerve MAP levels that were approximately 5-fold and 2-fold higher, respectively, than those observed with MAP alone. The silicone oil-induced ocular hypertension glaucoma mouse model was used for neuroprotection investigation. Compared to the MAP monotherapy, the MAP/BX combination led to > 21% greater ganglion cell complex thickness, > 7- fold axon preservation, and > 4-fold retinal ganglion cell survival. A comprehensive biosafety evaluation confirmed the safety of NeuProIO. The assessments of corneal thickness, RGC viability, and major organ histology revealed no adverse local or systemic effects. Taken together, NeuProIO has the potential to redefine glaucoma treatment, offering a more effective and long-lasting solution to preserving vision and improving patient outcomes.

Author(s): Lei Xu, Mu Li, Lin Qi, Tzu-Chen Wang, Dong Liu, Vimalin Jeyalatha Mani, Hsin-Yin Chuang, Qingbo Yang, Ruipu Mu, Samira Mahdi, Da Huang, Honglan Shi, Yang Hu, Hu Yang

Journal: Chemical Engineering Journal

Doi: https://doi.org/10.1016/j.cej.2026.173145

Link: https://www.sciencedirect.com/science/article/abs/pii/S1385894726006042

Experimental Paper of the Month manager: Nestor Ventura-Abreu

Editors in Chief: Francesco Oddone, Manuele Michelessi