Eudragit Films as Carriers of Lipoic Acid for Transcorneal Permeability

Abstract

Diabetes mellitus (DM) is a highly prevalent disease affecting almost 10% of the world population; it is characterized by acute and chronic conditions. Diabetic patients have twenty-five times higher risk of going blind and developing cataracts early than the general population. Alpha-lipoic acid (LA) is a highly valuable natural antioxidant for the prevention and treatment of ophthalmic complications, such as diabetic keratopathy and retinopathy. However, its applicability is limited due to its low solubility in water; therefore, suitable systems are required for its formulation. In this work we developed an erodible insert based on Eudragit E100 (E PO) and Lipoic Acid (LA) for the delivery of this compound for the preventive treatment of ocular diseases especially in diabetic patients. Film evaluation was carried out by mechanical and thermal properties, mucoadhesivity, drug release, dynamic light scattering and corneal permeability as the concentration of LA increased. It was shown that upon LA release, it forms nanoparticles in combination with E PO that favor corneal permeation and LA retention in the cornea. These E PO-LA films also resulted non-irritable hence they are promising for their application in the treatment of ocular diseases.

Diabetic Keratopathy: Redox Signaling Pathways and Therapeutic Prospects

“…In patients with diabetic DED, eye drops based on a combination of α-lipoic acid and hydroxy-propyl-methylcellulose were shown to improve the effectiveness of the therapy and self-regeneration, improving corneal defects [148]. Intriguingly, a combination of α-lipoic acid with Eudragit E100 as a carrier molecule enhanced corneal permeation, and thereby α-lipoic acid delivery, favoring its retention in the cornea [149].…”

Parallelism and non-parallelism in diabetic nephropathy and diabetic retinopathy

“…α-Lipoic acid (ALA) is a potent antioxidant ( 170 – 172 ) and is valuable in preventing and treating ocular complications such as diabetic keratopathy and DR ( 170 , 173 , 174 ). ALA has insulin-mimetic and anti-inflammatory activities ( 175 ), which increase insulin sensitivity ( 176 ), prevent retinal lipid peroxidation in early diabetes ( 177 ), inhibit the activation of NF-κB induced by late glycosylation end products in endothelial cells ( 178 ), and inhibit apoptosis in retinal capillary cells ( 179 ), thereby controlling the development of DR. ALA attenuates oxidative stress by regulating the expression of enzymes involved in the formation of reactive oxygen species ( 180 ), prevents glomerular thylakoid matrix expansion ( 181 ), inhibits diabetic renal fibrosis by improving mitochondrial function and regulating the expression and activation of isotretinoin receptor α (RXRα) ( 182 ), and protects the kidneys by possibly inhibiting neutrophil infiltration, modulating inflammatory mediators ( 183 ), and delaying the development of DN.…”