Ballistic delivery of compounds to inner layers of the cornea is limited by tough mechanical properties of stromal tissue

Abstract

The barrier characteristics of the cornea are interrogated using the impact of micro-particles into ex vivo porcine cornea. Using a commercial gene gun (BioRad; PDS1000), microparticles were accelerated and made to embed in target materials: either ballistic gelatin as a reference or corneal tissue. Statistical analysis of penetration of polydisperse spherical microparticles (5–22 μm dia.) with density of 2.5 g/cc, 4.2 g/cc, and 7.8 g/cc (soda-lime glass, barium-titanate glass and stainless steel; more limited examination of 1.1 g/cc polyethylene and 19.2 g/cc tungsten) spanned almost two decades in kinetic energy. Penetration profiles in ballistic gelatin show that the particle embedding depth is sensitive to particle size and density. In the cornea, penetration is a weak function of size and density, and the corneal stroma is an effective stopping medium for high velocity microparticles. Despite the high water content of corneal tissue (76% w/w) compared to the stratum corneum of skin (40% w/w), the resistance to penetration of the cornea is comparable to what is seen in previous research of penetration in skin tissue. Using low density polymer particles with a therapeutic agent payload, it is demonstrated that bulk material can be ballistically delivered to the central 1 cm2 of the corneal epithelium in an even layer with high bioavailability of therapeutic compound.