Emulsan-based Drug Delivery Devices

DESCRIPTION (provided by applicant): Emulsans are a novel family of functionalized polysaccharides that can be extensively modified structurally leading to substantive changes in solution properties (emulsification) and biological responses in vitro (i.e., macrophage activation, TNF release) and in vivo (i.e., vaccine delivery). In addition, these polymers are 'natural' carriers of other macromolecules with high loading capacities (up to 23 wt %). Based on these features, our hypothesis for the proposed study is that structural analogs of these microbial exopolysaccharides, emulsans, can serve as novel drug delivery vehicles when formed into microparticles with alginate. The powerful combination of significant ligand binding capacity of these polymers, strong structural tailorability and native amphiphilicity (hydrophobic fatty acid side chains, hydrophilic polysaccharide main chain) will allow for exploration of drug delivery vehicles with unique properties. We know of no similar set of relevant properties available with other biomaterials being considered for drug delivery. We plan to use the highly selective biological routes presented in our preliminary data to prepare a group of well-defined emulsan structural analogs. This arsenal of 'structurally tailored' emulsans will then be used to demonstrate the efficacy of these polymers in microparticle format to bind high concentrations of protein and non-protein pharmaceutical compounds, and the ability of said particles to deliver the test compounds to an appropriate cell type. The proposed studies will provide the first indication of the efficacy of emulsan structural analogs as drug delivery vehicles. Furthermore, lead candidates will result from the study in preparation for future studies in vitro and in vivo of mechanism, optimization of delivery and targeting, and overall efficacy. This new direction builds off of our extensive understanding of physiological and genetic control of emulsan biosynthesis, as well as initial insight into cell interactions related to cytokine control.