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.
Recommended Citation
L. Xu and M. Li and L. Qi and T. C. Wang and D. Liu and V. J. Mani and H. Y. Chuang and Q. Yang and R. Mu and S. Mahdi and D. Huang and H. Shi and Y. Hu and H. Yang, "NeuProIO: A Dual-action Solid Drug Nanoparticle Topical Formulation for Simultaneous Intraocular Pressure Reduction and Neuroprotection for Glaucoma," Chemical Engineering Journal, vol. 530, article no. 173145, Elsevier, Feb 2026.
The definitive version is available at https://doi.org/10.1016/j.cej.2026.173145
Department(s)
Chemical and Biochemical Engineering
Publication Status
Full Text Access
Keywords and Phrases
Drug repurposing; Glaucoma; Intraocular pressure; Neuroprotection; Solid drug nanoparticle; Synergistic treatment
International Standard Serial Number (ISSN)
1385-8947
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2026 Elsevier, All rights reserved.
Publication Date
15 Feb 2026
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biomedical Engineering and Bioengineering Commons, Chemical Engineering Commons
Comments
National Institutes of Health, Grant R01EY035088