α-Lipoic Acid in Soluplus® Polymeric Nanomicelles for Ocular Treatment of Diabetes-Associated Corneal Diseases

α-Lipoic acid (ALA) is a powerful antioxidant valuable for prevention and treatment of ophthalmic complications such as diabetic keratopathy and retinopathy. The aim of this work was to develop micelle-based formulations that can enhance the solubility, stability, and corneal permeability of ALA. Co...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2016-09, Vol.105 (9), p.2855-2863
Main Authors: Alvarez-Rivera, Fernando, Fernández-Villanueva, David, Concheiro, Angel, Alvarez-Lorenzo, Carmen
Format: Article
Language:English
Subjects:
Administration, Ophthalmic
alpha-lipoic acid
Animals
Antioxidants - administration & dosage
Antioxidants - therapeutic use
Cattle
Chorioallantoic Membrane
Cornea - metabolism
Corneal Diseases - drug therapy
Corneal Diseases - etiology
Diabetes Complications - drug therapy
diabetic keratopathy
Drug Compounding
Freeze Drying
HET-CAM assay
micelle
Micelles
Nanoparticles
ophthalmic drug delivery
Permeability
Polyethylene Glycols
polymeric drug carrier
Polymers
Polyvinyls
Solubility
Thioctic Acid - administration & dosage
Thioctic Acid - therapeutic use
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Summary:α-Lipoic acid (ALA) is a powerful antioxidant valuable for prevention and treatment of ophthalmic complications such as diabetic keratopathy and retinopathy. The aim of this work was to develop micelle-based formulations that can enhance the solubility, stability, and corneal permeability of ALA. Compared to a conventional surfactant (sodium dioctylsulfosuccinate), Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol copolymer) led to smaller micelles (70-80 vs. 240-528 nm) with improved ability to solubilize ALA, maintaining ocular compatibility (Hens Egg Test on the Chorio-Allantoic Membrane). Soluplus nanomicelles enhanced more than 10-fold ALA solubility compared to common eye drops and withstood strong dilution in lachrymal fluid, filtration through sterilizing membranes, and freeze-drying. Interestingly, Soluplus nanomicelle formulation prepared with 1 or 2 mM block copolymer concentration exhibited in situ gelling capability and transformed into weak gels at 35°C, which is expected to increase corneal residence time. Bovine corneal permeability revealed that Soluplus nanomicelles notably enhanced ALA accumulation into the cornea as well as flux of drug toward the receptor chamber. Overall, these findings point out Soluplus nanomicelles as suitable carriers of ALA that may exhibit improved performance compared to currently available eye drop solutions.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2016.03.006