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Theranostics 2021; 11(11):5447-5463. doi:10.7150/thno.54525 This issue Cite

Research Paper

Harnessing the tunable cavity of nanoceria for enhancing Y-27632-mediated alleviation of ocular hypertension

Li-Jyuan Luo^1*, Duc Dung Nguyen^1*, Jui-Yang Lai^1,2,3,4✉

1. Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan.
2. Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
3. Department of Materials Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan.
4. Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan.
*These authors contributed equally to this work.

✉ Corresponding author: E-mail: jylaicgu.edu.tw.

Abstract

Background: Y-27632 is a potent ophthalmic drug for the treatment of ocular hypertension, a globally prevalent eye disease. However, the sustained delivery of Y-27632 by a therapeutic carrier to lesion sites located in the inner segments of the eye for effectively treating the ocular disorder still remains challenging.

Methods: To realize the goal, a strategy based on solvothermal-assisted deposition/infiltration in combination with surface modification is utilized to synthesize hollow mesoporous ceria nanoparticles (HMCNs) with tailorable shell thicknesses and drug release profiles. The shell thickness of HMCNs is rationally exploited for achieving sustained drug release and advanced therapeutic benefits.

Results: The shell thickness can regulate release profiles of Y-27632, displaying that thick and thin (~40 nm and ~10 nm) shelled HMCNs reveal burst release characteristics (within 2 days) or limited drug loading content (~10% for the 40 nm thick). As a compromise, the HMCNs with moderate shell thickness (~20 nm) possess the most sustained drug release over a period of 10 days. In a rabbit model of glaucoma, a single instillation of the optimized Y-27632-loaded HMCNs can effectively treat glaucoma for 10 days via simultaneously repairing the defected cornea (recovery of ~93% ATP1A1 mRNA levels), restoring the reduced thickness of outer nuclear layer to normal (~64 µm), and restoring ~86% of the impaired photoreceptor cells.

Conclusion: A comprehensive study on the importance of HMCN shell thickness in developing long-acting nano eye drops for the efficient management of glaucoma is proposed. The findings suggest a central role of nanobiomaterial structural engineering in developing the long-life eye drops for pharmacological treatment of intraocular diseases.

Keywords: ceria nanostructure, shell thickness, hollow carrier system, Y-27632, ocular therapeutics

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