NeuProIO: A dual-Action Solid Drug Nanoparticle Topical Formulation for Simultaneous Intraocular Pressure Reduction and Neuroprotection for Glaucoma. Chem Eng J 2026 Feb 15;530
Date
02/23/2026Pubmed ID
41726861Pubmed Central ID
PMC12919395DOI
10.1016/j.cej.2026.173145Scopus ID
2-s2.0-105029233905 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
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 corneal transport. Single topical dosing sustained an effective IOP control (15% IOP reduction or higher) for 72 h. 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. In silicone oil-induced ocular hypertension glaucoma mouse model, the MAP/BX combination exhibited significantly improved neuroprotection effects than MAP monotherapy, including >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, with assessments of corneal thickness, RGC viability, and major organ histology revealing 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 List
Xu L, Li M, Qi L, Wang TC, Liu D, Mani VJ, Chuang HY, Yang Q, Mu R, Mahdi S, Huang D, Shi H, Hu Y, Yang HAuthors
Hsin-Yin Chuang Postdoctoral Researcher in the Biomedical Engineering department at Medical College of WisconsinLei Xu PhD Postdoctoral Researcher in the Biomedical Engineering department at Medical College of Wisconsin
