Javad Behmadi
, Amiremad Kheirieh, Asma Mahmoudi, Mojtaba Abrishami, Seyed Ali Mousavi Shaegh, Amirhossein Abbasi, Bizhan Malaekeh-Nikouei
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Abstract
Objective(s): Different ocular diseases, such as diabetic retinopathy and cataracts, could be induced by oxidative stress. Alpha-lipoic acid (ALA) exhibits antioxidant activity; however, its low aqueous solubility limits its ophthalmic use.[U1] Cationic nano-emulsions (NEs) have emerged as an effective method to enhance the bioavailability of drugs, particularly those with low water solubility. Traditional methods for synthesizing nano-emulsions typically involve multiple steps. In contrast, deployment of the microfluidic technique enables nanoassembly of NEs in a single step through a micromixer with improved efficiency and minimized reagents. Materials and Methods: In this research, ALA cationic NEs were synthesized utilizing a microfluidic device, with variations in total flow rates. The resulting formulations were characterized based on their size. The formulation identified as the most optimal underwent further assessment regarding its physicochemical properties. Following accelerated stability assessments, animal studies were performed to evaluate the safety of the formulation. Results: The findings indicated a loading efficiency of 79.92% for the optimized formulation. The synthesized nanoparticles exhibited satisfactory characteristics in terms of pH, refractive index, osmolality, and rheological properties. Ex vivo release test revealed the formulation released up to 59.3% of ALA. Furthermore, ALA was detected in both vitreous and aqueous humor during in vivo experiments. The formulation successfully passed accelerated stability tests and demonstrated good tolerance in the ocular environment of rabbits throughout the animal study. Conclusion: The cationic ALA nanoemulsion synthesized by microfluidics demonstrates favorable characteristics, along with high stability and tolerability, which have proven beneficial for subsequent evaluations.