Development of novel carriers, prodrugs, and liposomes for molecular transport

This dissertation describes supramolecular and covalent conjugate approaches to drug delivery and demonstrates the fundamental design concepts of several novel drug delivery systems. The first approach involved the development of boronic acid carriers that facilitate the transport of saccharides across lipophilic membranes. Mechanistic studies revealed that under certain conditions glycopyranosides can be transported through bulk liquid organic membranes as either neutral trigonal boronate esters or ion-pairs containing anionic, tetrahedral boronace adducts. The rate of transport was found to be dependent on the stereochemistry of the diol groups within the glycopyranoside and in the order: cis-;The next approach to drug delivery involved the development of a novel class of prodrugs for nucleotide monophosphates. A short series of ionophore nucleotide conjugates was synthesized. It was hypothesized that the ubiquitous inward directed Na;The third area of investigation explored two ways of inducing allosteric transitions in amphiphilic lipids, (i) metal-mediated, and (ii) metathesis mediated. A series of 1,2-dicarboxylic acids were evaluated as the amphiphile scaffold. A large conformational transition was noted upon conversion of the imide to acid-amide. The applicability of such transitions as a liposomal disrupting trigger is discussed.