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
