Surface Analysis of Ilomastat Tissue Tablet Following Incubation in Simulated Aqueous Fluid

Abstract

Purpose: : Tissue tablets are being developed for use after glaucoma filtration surgery (GFS) to better modulate the scarring response. These tablets work by delivering a matrix metalloprotease inhibitor (Ilomastat) to the conjunctival tissues over a period of weeks. The surface characteristics of this tablet will have a direct effect on the drug release profile and efficacy. Using a rig model of the GFS bleb we have evaluated how the surface properties of our tissue-tablet changed following incubation with either PBS (pH 7.4) or HBBS and 10 % serum (pH 7.1) to model the aqueous fluid. We aim to understand how the surface properties of tablets may change during incubation to improve their pharmacokinetics.

Methods: : Tablets were incubated in a rig that simulates the glaucoma bleb with a flow rate of 2 µl/min. Tablets were either incubated in PBS or HBBS with serum (10 %). Atomic force microscopy (AFM) was used to determine topographic, adhesiveness and stiffness changes of the tablet both before and after being incubated in the rig. X-ray photonelectron spectroscopy (XPS) and Time-of-Flight Secondary Ion Mass Spectrometry (Tof-SIMS) were used to determine the change in the surface chemistry of tablets.

Results: : Incubation of tissue tablets with PBS for 24 hours led to a decrease in surface adhesiveness (from 22 nN to 9.7 nN), and a decrease in surface stiffness (from 6 GPa to 1.4 GPa) as measured with AFM. Incubating tablets with simulated aqueous fluid led to an accumulation of sulfur atoms (0.12 % atomic composition as determined by XPS) on the surface (suggesting protein adsorption, absent in non-incubated tablets). These data were supplemented by Tof-SIMS, which showed an increased deposition of sulfur and phosphate ions on the tablet surface.

Conclusions: : Incubation of Ilomastat tablets in either PBS or simulated aqueous fluid led to a dramatic change in surface stiffness and adhesiveness. In addition, the accumulation of sulfur on the surface suggests the adsorption of protein. These factors need to be taken into consideration when determining the kinetics of Ilomastat release.

Keywords: imaging/image analysis: non-clinical • wound healing • topography