Ultrasound-assisted gatifloxacin delivery in mouse cornea, in vivo

Abstract

Gatifloxacin is a 4th generation fluoroquinolone antibiotic used in clinic to prevent or treat ocular infection. One limitation of gatifloxacin is its relatively poor corneal penetration compared to other antibiotics, and the increase of its trans-corneal delivery would be beneficial to reduce the amount or frequency of daily dose. In this study, ultrasound treatment was applied to enhance the trans-corneal delivery of gatifloxacin without damage. Experiments were conducted on mouse eyes in both ex vivo and in vivo conditions, and the mouse eyes were treated with ultrasound waves for 5 minutes before the instillation of gatifloxacin ophthalmic solution. Gatifloxacin distribution in the cornea was measured by two-photon microscopy (TPM) imaging based on its intrinsic fluorescence. TPM images of ultrasound treated mouse corneas showed an initial increase of gatifloxacin on the corneal surface and then its subsequent penetration into the corneal epithelium below the surface at later time. Delivered gatifloxacin into the corneal epithelium by ultrasound treatment stayed for an extended time. The enhanced trans-corneal delivery of gatifloxacin was measured to be more than 20% from the analysis of TPM imaging. This study demonstrated the detail process of enhanced trans-corneal gatifloxacin delivery by ultrasound treatment.