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Angel Concheiro, Fernando Alvarez-Rivera, Angela Varela-Garcia, Carmen Alvarez-Lorenzo; α-Lipoic acid nanomicelles in solution and in contact lenses for diabetes-associated corneal diseases. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4441.
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© ARVO (1962-2015); The Authors (2016-present)
α-Lipoic acid (ALA) is a powerful antioxidant with valuable hypoglycaemic and corneal epithelium reparation properties. ALA is orally given for treatment of diabetic polyneuropathy, or as eye drops for corneal-conjunctival alterations associated to diabetic retinopathy. The aim of this work was to elucidate whether encapsulation of ALA in nanomicelles could enhance drug solubility and corneal permeability compared to eye drops, and whether the nanomicelles could be incorporated into contact lenses for sustained delivery.
Soluplus® nanomicelles (0.4-2.0 mM) were loaded with ALA by soaking in aqueous suspensions. Drug solubility, and stability of drug-loaded micelles against dilution and after filtration and freeze-drying were quantified spectrophotometrically. Ocular toxicity and corneal permeability were evaluated on chorio-allantoic membrane and bovine eyes according to HET-CAM and BCOP tests (n=3) using commercial eye drops as reference. Cumulative amounts of ALA in cornea and in receptor chamber were quantified using HPLC. Hydroxyethylmethacrylate-based hydrogels were synthesized and effects of incorporation of nanomicelles during and after polymerization on contact lens properties and drug release were evaluated.
Soluplus® nanomicelles efficiently encapsulated ALA increasing more than 10-fold apparent solubility compared to commercial eye drops. ALA-loaded micelles behaved as non-irritant and exhibited remarkably high physical stability against dilution, membrane sterilization, freeze-drying and reconstitution. Bovine corneal permeability tests carried out in vertical (Franz) diffusion cells revealed that the amounts of ALA that permeated into the cornea and that diffused towards the receptor medium were significantly larger for ALA-loaded nanomicelles (amount in cornea 14-fold greater; flux of 143.5 µg/cm2h with tlag of 0.56 h) than for the commercial eye drops (flux of 44.5 µg/cm2h with tlag of 0.95 h). ALA-loaded nanomicelles did not alter the properties of contact lenses.
Soluplus® nanomicelles can be pointed out as advantageous nanocarriers for ocular delivery of ALA in terms of enhanced drug flux through cornea and shorten lag time and feasibility of scale-up. Moreover, these nanocarriers could be used concomitantly with hydrogel contact lenses or incorporated into them without detrimental effects on the ocular properties of contact lenses.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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