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Synthesis and Evaluation of Dendritic Polymer Carriers for Chemotherapeutic and Imaging Applications

Abstract

Among the multitude of compounds capable of exerting a potentially therapeutic effect

on a diseased biological system, only a very select few happen to possess the stringent

pharmacokinetic profile required to be used in practice. In addition to being biologically active,

a potential drug candidate must also have good solubility in biological systems, reach its target

destination in adequate quantities to bring about the desired effect, and not cause a substantial

degree of harm to nontargeted areas of the body through toxicity or side reactions. These

requirements also apply to biological agents used in conjunction with treatment, such as

molecular diagnostic tools used for disease imaging and marking. Rather than simply discount

agents lacking ideal pharmacokinetics, polymeric drug delivery attempts to mask these

deficiencies by incorporating these small molecules into their structure, and in doing so create a

conjugate structure in which the favorable pharmacokinetic properties of the carrier mask the

unfavorable properties of the drug. In this work, the design, synthesis and potential uses and

benefits of a specific family of these carriers, pegylated dendrimers, is presented and discussed.

In the first chapter, the general principles of drug and imaging agent delivery via dendrimers and

other macromolecules are discussed, as well as the differences found among the various systems

commonly employed for this purpose. With a focus on dendrimers, this chapter will go on to

address the importance of fidelity to ideal molecular structure, synthetic tailorability, and optimal

pharmacokinetic profile in these systems, and how such aspects are installed or maintained with

minimal synthetic investment.

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