Electronic Thesis and Dissertation Repository

Characterization and Enhancement of Local Drug Delivery in Orthopaedic Infection

Tina Khazaee, The University of Western Ontario

Abstract

The delivery of antibiotics is an important component of therapy for orthopedic device-related infections (ODRI). In this study, we have investigated new techniques to characterize and enhance antibiotic delivery for ODRI. Characterization of small-molecule diffusion is essential to the development of drug-delivery systems. We have developed a quantitative, non-invasive, longitudinal, micro-CT technique to quantify the diffusion of small-molecules in an intact phantom. We employed a radio-opaque molecule (i.e., Iohexol) as a surrogate for commonly used antibiotics (e.g., Vancomycin). We characterized diffusion from a finite-core carrier into an agar, tissue-equivalent phantom. The estimate of the diffusion coefficient was derived from the analysis of radial diffusion distance of Iohexol and the cumulative release amount of this drug surrogate. This micro-CT method enabled us to describe the elution of small-molecules from enhanced carriers within a porous metal scaffold. To enhance antibiotic delivery, we designed and fabricated gyroid-based scaffolds with appropriate mechanical properties and filled with Iohexol-loaded carriers. Diffusion characteristics within the porous structures were evaluated using the micro-CT technique.