(688b) Synthetic Polyphenols for Drug Delivery

Polyphenols have been extensively researched as therapeutics but primarily as plant derived, low molecular weight compounds. We have designed synthetic polyphenols that mimic the structure of those that occur naturally. Specifically, we have been able to attach phenolic residues to polysaccharide scaffolds through the careful tuning of acyl transfer reaction conditions. By controlling the number of pendant phenolic groups we can design synthetic polymers with antioxidant power greater than what can be derived from natural sources. As water soluble polymers these can also be potentially targeted to sites of disease within the human body in ways unavailable to small molecules. We are investigating the unusually strong hydrogen bonding between polyphenols and poly(ethylene glycol) (PEG) as a way to form self-assembled, nanoscale drug carriers. By synthesizing synthetic polyphenols with controlled size and shape, better control over the PEG-polyphenol self-assembly process can be achieved. We are developing a combinatorial library of these structures that achieve the following goals: diameters < 200 nm, neutral surface charge, and the ability to be package small and large molecular weight chemotherapeutic agents. Preliminary results showed that the spontaneous complexation between the two polymers and resulting particle size could be controlled through polymer chain length and chain configuration. Our long term goal is to select compounds capable of targeting siRNA specifically to cancer cells.