Therapeutic Microparticles and Biolistic Drug-Delivery to the Cornea

Citation

Laccetti, Benjamin Joseph (2021) Therapeutic Microparticles and Biolistic Drug-Delivery to the Cornea. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/nf29-gy82. https://resolver.caltech.edu/CaltechTHESIS:10182020-133113205

Abstract

The ability to deliver therapeutic compounds to the cornea using high-velocity microparticles is assessed and a method to synthesize therapeutic particles suitable for the cornea is demonstrated. Using a commercial gene gun (BioRad; PDS1000), a pneumatic capillary gun, and custom biolistic technology, microparticles were accelerated and made to embed in target materials: either homogeneous gels or corneal tissue. In homogeneous gels, penetration was shown to be directly proportional to particle size and density. In contrast, penetration of microparticles into the cornea is insensitive to particle size and density: varying the sectional density by 680% failed to penetrate beyond the epithelium (ca. 50 microns). The corneal epithelium exhibits two distinct kinetic energy thresholds that must be exceeded to first embed particles in the epithelium (rather than stopping on its anterior surface) and second to embed particles in the stroma (rather than stopping at the posterior surface of the epithelium). Penetration profiles show that the stroma is a highly effective stopping medium for high velocity microparticles. Despite the high water content of corneal tissue (76 w%) compared to the stratum corneum of skin (40 w%), the resistance to penetration of the cornea is comparable to literature values for skin. Ideal particles for drug delivery to the cornea would dissolve away completely, leaving no residue that might scatter light. With a vibrating orifice aerosol generator and a temperature-controlled column, 30-50 µm particles were composed of 1% Eosin Y with poly(ethylene glycol). Using low density polymer particles with a therapeutic agent payload, it was demonstrated that bulk material can be ballistically delivered to the central 1 cm² of the corneal epithelium rapidly, in an even, quantifiable layer.

Thesis Files