RT Journal Article
T1 Enhancement in corneal permeability of riboflavin using cyclodextrin derivates complexes as a previous step to transepithelial cross-linking
A1 Conde Penedo, Andrea
A1 Díaz Tomé, Victoria
A1 Fernández Ferreiro, Anxo
A1 González Barcia, Miguel
A1 Otero Espinar, Francisco Javier
K1 Corneal drug delivery
K1 Cornea
K1 Corneal epithelium
K1 Cyclodextrin
K1 Riboflavin
K1 Keratoconus
K1 Corneal cross-linking
AB Corneal 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
PB Elsevier
YR 2021
FD 2021
LK http://hdl.handle.net/10347/27525
UL http://hdl.handle.net/10347/27525
LA eng
NO European Journal of Pharmaceutics and Biopharmaceutics 162 (2021) 12-22
DS Minerva
RD 27 abr 2026