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    Enhanced Transepithelial Riboflavin Delivery Across the Cornea Using Magnetic Nanocarriers
    (Mary Ann Liebert, Inc, 2025) Coskun, Alaaddin; Senturk, Fatih; Turan, Eylem
    Purpose: Keratoconus is a progressive corneal ectasia characterized by irregular astigmatism, leading to corneal scarring and decreased vision. Corneal cross-linking (CXL) is the standard treatment to halt disease progression, but its effectiveness in transepithelial (epithelium-on, epi-on) approaches is limited by the low permeability of the corneal epithelium to riboflavin (Rb). This study aimed to enhance transepithelial Rb penetration in ex vivo bovine corneas using Rb-modified tannic acid-coated superparamagnetic iron oxide nanoparticles (Rb-TA-SPIONs) under an external magnetic field.Methods: SPIONs were synthesized via co-precipitation, modified with TA and Rb, and characterized by physicochemical techniques. The average size of the Rb-TA-SPIONs was 46 +/- 5.3 nm, with a saturation magnetization of 55.9 emu/g. Ex vivo experiments involved the application of 0.1% Rb to bovine corneas, and penetration was evaluated under epi-on conditions with iontophoresis (1-5 mA, 5 min). In addition, a 0.1% Rb-containing nanocarrier solution was tested under magnetic fields of 1-300 Gauss.Results: Results showed increased Rb penetration with rising electric current density and Rb-TA-SPION penetration with stronger magnetic fields, compared with epi-on control groups. Specifically, Rb penetration increased from 0.036% (P <= 0.01) at 1 mA to 0.059% (P <= 0.001) at 5 mA in the iontophoresis group and from 0.035% (P <= 0.001) at 1 G to 0.054% (P <= 0.001) at 300 G in the magnetic group.Conclusion: These findings indicate that magnetic nanoparticle-assisted Rb delivery, guided by an external magnetic field, could improve potential CXL efficacy by enhancing Rb penetration and corneal permeability.