A Promising Ocular Delivery Approach of a Novel Nano-based Multifunctional System

Abstract

Aim: Delivery of ophthalmic drugs to the interior parts of the eye remains a huge challenge because of the well-known static and dynamic ocular barriers. Nanoceria (NC), exhibits unique auto-regenerative antioxidant capacity, leading to its wide applications in the management of various oxidative stress-related diseases, especially ocular diseases. Besides, NC could be adopted as a nanocarrier to deliver specific drug to ocular tissues. Herein, the current study presents a novel multifunctional Metformin-loaded cerium oxide nanoparticles with potential synergistic ophthalmic activity for topical ocular delivery in a challenging drug repurposing approach for intraocular targeted and sustained delivery of metformin (MET), that possesses considerable anti-angiogenic and anti-inflammatory effects on retinal vasculature. Methodology: Glycol chitosan-coated negatively charged NC particles were developed and loaded into an in-situ gel/film-forming system to overcome the inconvenience and eye protective mechanisms that limit the ocular availability after the topical application of traditional ocular delivery systems. The developed particles were evaluated for entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), Fourier-transform infrared spectroscopy, morphology, in vitro release, and in vivo ocular hypertension model on rabbits. Results: Results revealed that MET-loaded NC exhibited adequate EE% (62±3.2%), along with a PS of 222.2±11.25 nm which is ideal for the rapid penetration through vitreous gel, ZP of -23.9±2.67 mV and drug prolonged release behaviours from the in situ gel/film-forming system of MET-loaded NC followed by MET-loaded NC compared to free MET. Regarding in-vivo study results, MET-loaded NC in film forming solution revealed a significant reduction in IOP compared to free MET and plain NC in film forming solution. Conclusion: These findings indicated that the targeted co-delivery of MET using NC may offer a promising versatile therapy option for the treatment of vision threatening ocular diseases