Purpose: To investigate the efficacy and safety of a new cyclosporine A (CsA) delivery system using contact lenses (CLs) for the treatment of experimental dry eye (EDE).
Methods: CsA-laden porous carriers and CsA-eluting CLs were fabricated using the supercritical fluid technique. The release of CsA from carriers and CLs was investigated using high-performance liquid chromatography. The CsA concentrations in the cornea, conjunctiva, and crystalline lens of rabbits were measured. Dry eye was induced using 0.1% benzalkonium chloride in rabbits, which were subdivided into the normal, EDE, balanced salt solution (BSS), 0.05% CsA, hydrogel CL, or CsA-CL groups. Tear volume, tear film break-up time (TBUT), and corneal staining scores were measured at 1 and 2 weeks after treatment. Periodic acid-Schiff staining for the evaluation of conjunctival goblet cell density was performed at 2 weeks. Interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and interferon-γ levels in the conjunctiva were measured using enzyme-linked immune-sorbent assay.
Results: The porous carrier showed the release of drug. CsA-eluting CLs showed initial burst and sustained release of CsA until 48 h. The concentration of CsA elevated in the cornea, conjunctiva, and lens until 48 h after application of CsA-CLs. The CsA-CL group showed significantly higher tear volume, TBUT, and lower corneal staining scores compared to the other groups (p < 0.05). Goblet cell density was significantly higher in the CsA-CL group compared to the other groups. The CsA-CLs group showed a lower level of IL-1β than the BSS and soft CL groups (p < 0.01), and a lower level of IFN-γ than the other groups (all p < 0.01).
Conclusions: The newly designed CsA-eluting CLs released drug continuously and showed good penetration in the eye. In addition, the use of CsA-eluting CLs improved clinical parameters and conjunctival goblet cell density and decreased inflammatory cytokines.
Keywords: Cyclosporine A; contact lens; drug delivery; dry eye disease; supercritical fluid technique.