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

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 (similar to 40 nm and similar to 10 nm) shelled HMCNs reveal burst release characteristics (within 2 days) or limited drug loading content (similar to 10% for the 40 nm thick). As a compromise, the HMCNs with moderate shell thickness (similar to 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 similar to 93% ATP1A1 mRNA levels), restoring the reduced thickness of outer nuclear layer to normal (similar to 64 mu m), and restoring similar to 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.

Automated summary

By controlling the shell thickness of hollow mesoporous ceria nanoparticles (HMCNs), sustained release of Y-27632 was achieved, demonstrating effective treatment for up to 10 days in a rabbit model of glaucoma.