Tissue-on-Tissue Testing of Dry Eye Formulations for Reduction of Bioadhesion

Abstract

Glutaraldehyde-preserved, human umbilical cord vein graft (UCVG) was selected as a stable surrogate tissue source for testing of bioadhesion-reducing lubricants. Bioadhesion, as manifested in tissue-on-tissue friction coefficients of 0.2–0.4 for saline-lubricated UCVG, was quantitatively and persistently reduced after the instillation of a single aliquot of an ophthalmic “artificial tears” formulation containing active demulcents polyethylene glycol (PEG400) and propylene glycol (PG), as well as a gellable hydroxypropyl guar (HP Guar) in a borate-buffered solution between the “blinking” tissues. Reduced adhesion was maintained (was “substantive”), even after rinsing excess lubricant from the surfaces. Comparative tests with tissue-on-solid, and solid-on-solid, similarly lubricated couples point to a potentially unique mechanism that involves macromolecules modifying the tissue phases to provide rinse-resistant lubricity and surface protection in articulated tissue-to-tissue interfaces. Results for tissue-on-tissue couples were obtained in laboratory trials utilizing a reciprocating pin-on-disc type friction/wear test device articulating preserved human umbilical cord vein segments under increasing loads, and again after saline rinsing to determine persistence of the friction-reducing effects. A single confirmatory test using donated human cornea against vein graft tissue showed the lowest coefficient of friction, below 0.05, for the “artificial tears” formulation. Mechanistic studies employing the same test device and protocol for metal oxide (germanium)-on-metal oxide couples, as well as for metal oxide-on-tissue couples, indicated that simple increases in viscosity were not the likely sources of friction reduction, and revealed frictional values higher than measured for the similarly lubricated tissue-on-tissue couples. Thus, formulation development to minimize bioadhesion requires that appropriate simulations be used to obtain clinically predictive data for circumstances of liquid uptake into the tissues, resultant tissue swelling, and binding to impermeable adjacent materials.

Keywords:

• Cornea
• Friction
• Guar
• Lubrication
• Tears
• Tissue

ACKNOWLEDGMENT

This project was funded by Alcon Research Ltd. The authors thank Robert L. Forsberg and James M. Fick (University at Buffalo) for their technical contributions.

Notes

∗negative value → reduction in friction relative to initial condition.

positive value → increase in friction relative to initial condition.