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dc.contributor.authorConde Penedo, Andrea
dc.contributor.authorDíaz Tomé, Victoria
dc.contributor.authorFernández Ferreiro, Anxo
dc.contributor.authorGonzález Barcia, Miguel
dc.contributor.authorOtero Espinar, Francisco Javier
dc.identifier.citationEuropean Journal of Pharmaceutics and Biopharmaceutics 162 (2021) 12-22
dc.description.abstractCorneal cross-linking has been described as an effective treatment to slow the progression of keratoconus. The standard protocol entails corneal epithelial removal to allow the diffusion of riboflavin into the stroma. Although, de-epithelization can generate risks or complications that transepithelial cross-linking tries to solve or avoid. Different formulations were developed after verifying that hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobuthylether-β-cyclodextrin (SBEβCD) in a 20% concentration, increased the solubility of practically insoluble in water drugs such as riboflavin from 0.12 mg/mL to 0.35 mg/mL and 0.29 mg/mL respectively. These values were higher when chitosan and arginine were added to the formulation, showing solubility of 0.78 mg/mL when HPβCD concentration was not modified. Ex vivo corneal permeability was measured after having kept in contact bovine corneas with intact epithelium for 5 h with the 0.1 mg/mL riboflavin solution, the formulations developed and a reproduced nanoemulsion from another work. Riboflavin’s permeability was increased when cyclodextrins, chitosan, and arginine were part of the formulations, compared to the control drug solution. The best permeability coefficient was reached when riboflavin was combined with 40% (w/v) HPβCD, 0.5% (w/w) arginine, and 0.5% (w/w) chitosan. After having carried out toxicity studies as bovine corneal opacity and permeability (BCOP) and Heńs Egg Test - Chorioallantoic Membrane Test (HET-CAM) it was verified that both, the active ingredients and the excipients of the different formulations were not harmful without generating irritation, loss of transparency or corneal permeability alterations. The results show the great potential of the ocular developed solution for their use in transepithelial cross-linking for keratoconus treatment
dc.rights© 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (
dc.subjectCorneal drug delivery
dc.subjectCorneal epithelium
dc.subjectCorneal cross-linking
dc.titleEnhancement in corneal permeability of riboflavin using cyclodextrin derivates complexes as a previous step to transepithelial cross-linking
dc.contributor.affiliationUniversidade de Santiago de Compostela. Departamento de Farmacoloxía
dc.contributor.affiliationUniversidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica

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© 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (
Except where otherwise noted, this item's license is described as  © 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (

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