Novel approaches to dendrimer based radiopharmaceutical imaging agents and drug delivery systems

Abstract

The work reported in this thesis details two novel approaches towards the use of poly(amidoamine) (PAMAM) dendrimers for medicinal applications. The introduction contains a brief overview on the synthesis and properties of dendrimers, focusing in particular on PAMAM dendrimers and the growing interest in their use as polymer therapeutics. The second part of the introduction contains an overview of the role of Tc99m in nuclear medicine. The final part of the introduction gives an explanation of the genetic disorder, cystic fibrosis, concentrating on the degenerative lung disease associated with the disease and the role neutrophil elastase has in the degeneration of the lung. The next chapter then proceeds to describe the preparation of 4^ and 5* generation PAMAM dendrimers with dioctylamine surface groups. These surface modified dendrimers are reported as potential NaTc99mO4 complexation systems for potential application as radiopharmaceutical agents for use in lung imaging. The next chapter describes the preparation of PAMAM dendrimers with P-lactam and saccharine-based inhibitors linked to the surface. These modified dendrimers are shown to inhibit intracellular neutrophil elastase in samples of human blood. The results indicate that the modified dendrimers could potentially be used to reduce the extent of lung damage in a cystic fibrosis patient and improve both their quality of life and life expectancy.

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