Ex Vivo Biodistribution of α-Lipoic Acid in the Eye Using Ocular Inserts: A Novel Strategy for Retinal Antioxidant Therapy.

Purpose: This study aimed to investigate if topically administered natural occurring antioxidant, alpha-lipoic acid (ALA) incorporated in beta-cyclodextrins (β-CDs) (molar ratio 1:1 to increase ALA solubility and stability), can reach the tissues in the posterior segment of the eye, especially the retina. Design: Ex vivo experimental study. Subjects: Excised porcine eyes. Methods: Two ocular inserts (F1 and F2) containing ALA in β-CD were prepared to be applied over the cornea and over the sclera. In addition, a 1 mg/mL solution of ALA in β-CD was also applied. All formulations were administered to pigs' eyes for 8 hours. After treatment, the eyes were rinsed with phosphate-buffered saline, wrapped in parafilm to preserve their morphology, and stored at -80°C for 12 hours. The frozen eyes were then surgically dissected to separate the different ocular structures. Alpha-lipoic acid was extracted from the structures after soaking in a mixture of acetonitrile:water (80:20, v/v) for 12 hours. The samples were subsequently filtered, and the concentration of ALA was quantified using a validated high-performance liquid chromatography method. Main Outcome Measures: Characterization of the inserts and ALA concentration in ocular tissues. Results: Alpha-lipoic acid in solution or inserts was not found to cause irritation using the hen's egg test on chorioallantoic membrane. Using different formulations, ALA was detected in all ocular tissues except the iris. Higher amounts of ALA were detected when the molecule was applied via inserts than when applied in solution, likely due to the inserts prolonged contact time, which enhances biodistribution throughout the eye. After 8 hours, up to 4.0% of ALA delivered via corneal inserts reached the retina. In contrast, higher concentrations of ALA in the sclera and vitreous humor were detected when administration was through scleral inserts. Conclusions: These findings indicate that under ex vivo conditions, ALA applied in solution or via inserts can effectively diffuse through the cornea and sclera, reaching the posterior segment of the eye and the retina. This evidence supports the feasibility of conducting in vivo studies to further explore the potential of topically administered ALA to reduce ocular disorder complications. Financial Disclosures: The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.