Design and manufacture of functional titanium–palladium devices for the activation of anti-cancer prodrugs

2019-06-27T08:23:44Z (GMT) by Mohammad Alqahtani
National health organisations and authorities have reported an increment in death cases due to cancer. To overcome this issue and improve the survival rate, it is needed to find new clinical methods, early diagnoses techniques and treatments. Radiation and chemotherapy have been used for years to treat cancer. However, these types of treatments have serious side effects such as hair loosing, the mortality of healthy cells and other organs. A new treatment based on prodrugs therapy is in development with the intention to reduce these side effects or to replace the harmful treatments completely. Prodrug treatments need an activation agent, i.e. a catalyst, to convert the prodrug delivered to the cancerous cells to an active drug in-situ. Metals such as palladium can be used as a catalyst to activate the prodrug in targeted cancer cells.
In this PhD study, the research was divided into two major aspects. The first aspect was to design and manufacture a catalyst carrier with specific properties and specifications such as biocompatibility of the materials used as the carrier, suitable mechanical properties to withstand physiological loads and conditions, and cost efficiency of the production. Two different manufacturing methods were used, Powder Metallurgy technique and Arc Melting technique, to achieve the optimal fabrication method. The carriers were characterised via XRD, SEM, EDS, DSC methods and mechanical tests to ensure the carrier meets the requirements. In the second stage, the carriers were coated with Palladium in its metallic state (i.e. Pd0). The coating was required to meet the requirements of being unalloyed, pure and free of any contamination, and its deposition cost and time effective. Four coating methods were employed. Powder Metallurgy technique and sintering (with and without space holder), Magnetron Sputtering, Pulsed Laser Deposition and Supersonic Beam Cluster Deposition methods were used to apply Palladium coating onto the carriers. The coating was characterised by XPS, XRD, FIB, XRF, SEM, EDS, biochemical and in-situ biological tests.
The results obtained confirmed that the devices achieve high biocompatibility of the materials, and an excellent superelasticity can withstand the loads inside the human body. Also, the Magnetron sputtering methods as a coating method demonstrated it is the most effective for achieving a uniform and long-lasting deposited layer. The devices were able to activate a clinically approved prodrug.