Iontophoretic delivery of caspofungin acetate to the cornea and sclera and its intracorneal biodistribution

Caspofungin (CAS) is a potent antifungal agent belonging to the echinocandin family. It is a water-soluble dication at physiological pH, making it a good candidate for iontophoresis. Intracorneal iontophoretic delivery and biodistribution of CAS and its electrically assisted transport into the sclera were investigated as a function of experimental conditions, including donor concentration (1, 5 and 10 mg/mL) and application time (5 and 20 min) using an in-house set-up (with Ag/AgCl electrodes) and a marketed iontophoretic applicator (Iontofor CXL®) that used inert (stainless steel) electrodes. CAS deposition after passive delivery for 20 min (10 mg/mL) was 64.9 ± 23.7 μg/cm² and 370.9 ± 67.49 μg/cm² in the cornea and sclera, respectively. This increased by ∼14- and 3-fold, respectively, after iontophoresis at current densities of 1.5 mA/cm² and 3.5 mA/cm², respectively, for corneal and scleral application using the in-house set-up. The same trends were observed in the Iontofor CXL® studies - although the superiority of iontophoresis over passive delivery was less pronounced due to the electrolysis of water at the anode and the creation of competing hydroxonium ions in the anodal compartment. Intracorneal biodistribution studies showed that after iontophoresis using the Iontofor CXL® (1 mA, 20 min) significantly greater amounts of CAS were present in each lamella as compared to passive delivery and higher CAS concentrations were also achieved in the stroma and endothelium. CAS concentrations in the epithelium, stroma and endothelium after short-duration iontophoresis (1 mA for 5 min) - were > 100-fold higher than the MIC₉₀ reported for <i>Candida albicans</i> and <i>Aspergillus</i> spp.