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. 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.
Departamento de Farmacia y Tecnología Farmacéutica (Group GI-1645), Facultad de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain.
Fernando
F
Alvarez-Rivera
Departamento de Farmacia y Tecnología Farmacéutica (Group GI-1645), Facultad de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain.
David
D
Fernández-Villanueva
Departamento de Farmacia y Tecnología Farmacéutica (Group GI-1645), Facultad de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain.
Angel
A
Concheiro
Departamento de Farmacia y Tecnología Farmacéutica (Group GI-1645), Facultad de Farmacia, Universidade de Santiago de Compostela, Santiago de Compostela 15782, Spain. Electronic address: Carmen.alvarez.lorenzo@usc.es.
Carmen
C
Alvarez-Lorenzo
D060433:Administration, Ophthalmic; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002417:Cattle; D049033:Chorioallantoic Membrane; D003315:Cornea / Q000378:metabolism; D003316:Corneal Diseases / Q000188:drug therapy* / Q000209:etiology; D048909:Diabetes Complications / Q000188:drug therapy*; D004339:Drug Compounding; D005612:Freeze Drying; D008823:Micelles; D053758:Nanoparticles; D010539:Permeability; D011092:Polyethylene Glycols; D011108:Polymers; D011145:Polyvinyls; D012995:Solubility; D008063:Thioctic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
D000975:Antioxidants; D008823:Micelles; D011108:Polymers; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D008063:Thioctic Acid
HET-CAM assay; alpha-lipoic acid; diabetic keratopathy; micelle; ophthalmic drug delivery; permeability; polymeric drug carrier; solubility