Design and Implementation of a Microparticle Delivery Device for the Cornea

Citation

Ko, Dennis Lok (2024) Design and Implementation of a Microparticle Delivery Device for the Cornea. Dissertation (Ph.D.), California Institute of Technology. https://resolver.caltech.edu/CaltechTHESIS:02072024-100209417

Abstract

Biolistic drug delivery offers an alternative path for delivering therapeutics into the cornea. Until now, none of the commercially available gene guns are suitable for clinical delivery of therapeutics due to tissue damage caused by high speed gas used to accelerate microparticles. Here, we demonstrated the use of a device that both eliminates the exit gas, only allowing high speed particles through, and one that works in a clinical setting.

Microparticles ranging from 5 to 22 μm were accelerated and delivered into both the agarose gels and ex vivo corneas. In gels, we found that normalized penetration depth was proportional to particle diameter and density. As the standoff distance between the device and the target increased, more particles were left stranded at the surface, as their penetrating power decreased, and their dispersion from the center of mass on the target increased. The orifice size served to control both the number of particles and the amount of exit gas. Increasing the inlet pressure did not a show significant increase in the penetration depth of microparticles.

In the cornea, we found that we were able to use our device to deliver particles into both the epithelium and the stroma, although only higher density particles were able to enter the stroma. There was little to no damage to the cornea due to particle delivery. If epithelial defects were detected in the cornea due to particle penetration, they were quickly resolved within 30 minutes. Our device demonstrated performance (penetration depth) comparable to previous biolistic delivery methods in the cornea, while also maintaining clinical relevance by eliminating exit gas flow.

Thesis Files