Systemic drug administration (i.e., intravenous injection), leading to drug circulation throughout the body can be associated with adverse side effects. Alternatively, localized drug delivery systems have been developed to focus drug concentrations at target sites. This method of delivery has been widely accepted in orthopedic infection management where the poor blood supply hampers antibiotics from reaching the infected site. Antibiotic-loaded bone cement beads have been approved for clinical delivery systems for the localized treatment of bone infections (osteomyelitis). The beads, however, have some shortcomings such as incompatibility with some antibiotics, and poor drug elution, which relies on unregulated passive diffusion.
This dissertation proposes an on-demand drug delivery device that can control the release pattern using a controlled magnetic field application. The drug delivery device has the same configuration as conventional bone cement beads. It provides a sustained antibiotic discharge through a PMMA shell with multiple holes, while incorporating a magnetic porous PDMS at its core to manage the release profile via external magnetic fields.
The magnetic sponge’s magneto-mechanical properties are investigated under non-uniform magnetic fields. Unlike proposed models that explore the effect of uniform magnetic fields, this study presents an analytical model that demonstrates the magnetic sponge response to the magnetic field gradient. The findings of this study and the development of the drug delivery device can provide adjustable released content controlled by the strength of the applied magnetic field. The in vitro experiments confirm the antibacterial efficacy of discharged gentamicin and silver against both gram-positive and gram-negative bacteria with extended bactericidal activity up to six days after drug combination. The ex vivo assessment demonstrated a successful drug discharge upon implantation with a controllable release profile using a magnet.
Furthermore, to address the increasingly prevalent problem of antibiotic-resistant bacteria, a synergy study was conducted on gentamicin and silver nitrate. The results showed a significant improvement in the antibacterial efficiency once the two agents are combined, inhibiting the growth of MRSA and E. coli by more than 3log10CFU/mL. Exploiting the drug combination therapy in conjunction with a controllable localized drug delivery device may provide a more efficient therapy for treating osteomyelitis.Applied Science, Faculty ofBiomedical Engineering, School ofGraduat
