Purpose: α-Lipoic acid (LA) aqueous formulations were studied for nonoral administration, including intravitreal and intraperitoneal preparations and topical eyedrops. The potential retinoprotective effects of these LA preparations were also evaluated in streptozotocin (STZ)-induced diabetic rats for screening better delivery systems of LA.
Methods: Four LA liquid preparations were prepared and investigated. The short-term accelerated stabilities of LA preparations were investigated at 3 temperatures: 50°C, 70°C, and 90°C. The time courses of LA degradation in the preparations were determined by high-performance liquid chromatography. Furthermore, the potential therapeutic effects of LA preparations in a STZ-induced diabetic rat model were assessed by vitreous fluorophotometry to evaluate the fluorescein leakage from ocular vascular vessels into the vitreous. Capillary lesion in the retina was also examined using hematoxylin-eosin-stained microsections.
Results: LA in an aqueous solution was rapidly degraded with the activation energy of 10.4 kcal/mol. The 3 LA preparations had shelf lives of ∼1 month at 25°C. These formulations significantly reduced the vitreous fluorescein level in STZ-induced diabetic rats as evaluated by the fluorescein leakage after tail vein injection. Capillary lesions in the retina of the diabetic rats were remarkably reduced by nonoral administration, particularly the intraperitoneal injection (30 mg/kg/day).
Conclusions: LA could be developed as aqueous preparations with suitable stability for short-term use in nonoral administration. LA preparations could be administered intravitreally or intraperitoneally to reduce ocular microvascular complications, such as retinopathy, in diabetic patients.