Pt(IV) anticancer prodrugs and liposomal encapsulation

Thesis

This work describes the development of several photoactivatable platinum based anticancer prodrugs. The use of liposomes as a method of drug encapsulation for a known platinum complex is also explored. Finally, the synthesis of a microbubble-liposome conjugated system and the sonoluminescence effect of microbubbles are assessed. Chapter 1 discusses the fundamental properties of platinum, how it is currently utilised in chemotherapy, and the potential benefits of light-activated platinum compounds. The use of liposomes in medicine, with particular focus on drug encapsulation, is discussed in detail. The clinical applications of microbubbles are also explored. Chapter 2 describes the development and characterisation of two novel photoactivatable PtIV complexes. The solubilities, photochemical properties and pKa values of these compounds are compared to those of two previously reported complexes. Chapter 3 reviews the use of liposomes for the encapsulation of the drug iproplatin, with exploration of the best active loading method for this compound, and how the composition of the liposomes can be adapted to improve drug retention. Chapter 4 discusses the optimisation of synthesis for a conjugated microbubble-liposome drug delivery system. The phenomenom of sonoluminescence, and it’s potential use for activating photosensitive compounds is also explored. Chapter 5 describes the conclusions for this work, and what the next steps of this research would involve. Chapter 6 provides the experimental procedures and synthetic methods used in this work.

Authors: Marsh, L

• DOI: 10.5287/ora-pzyjaayvv
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: platinum; photoactivation; anticancer; microbubbles; liposomes; DIPG; prodrugs
• Subjects: platinum compounds; microbubbles; photochemotherapy; liposomes