Nanoscale amphiphilic macromolecules (AMs) comprised of a sugar backbone, branched aliphatic chains, and a hydrophilic poly(ethylene glycol) (PEG) tail have shown promise as bioactive delivery systems. These AMs can self-assemble into thermodynamically stable micelles or can be formulated into kinetically trapped nanoparticles, providing the ability to deliver hydrophobic drugs. Furthermore, such AMs have exhibited inherent bioactivity against atherosclerosis, a leading cause of cardiovascular disease, through interacting with macrophage scavenger receptors. As the hydrophobic portion of AMs enables their association with both hydrophobic drugs and receptor binding pockets, manipulation of the aliphatic chain structure may strengthen AMs' interactions with specific target sites or drug molecules and thus enhance their biomedical potential. To this end, novel AMs were synthesized with heteroatom-containing, end-modified aliphatic chains and their physicochemical and biological properties assessed. Within these studies, dibenzyl L-tartrate hydroxyl groups were acylated with modified aliphatic chains, and the resulting intermediate was deprotected to give a sugar-based hydrophobic segment, which was subsequently PEGylated to yield the final AM. The AM structure was confirmed by nuclear magnetic resonance spectroscopy and gel permeation chromatography. Fluorescence spectroscopy and dynamic light scattering were used to determine AM critical micelle concentrations and hydrodynamic diameters, respectively. Upon complete physicochemical characterization, the novel AMs' bioactivities were assessed to measure their potential as delivery vehicles and their abilities to interact with macrophage scavenger receptors. Figure 1. <img src='https://acs-archive-assets2.s3.amazonaws.com/239nm/uploads/6962_acs_figure.jpg' alt='' />

Amphiphilic macromolecules with novel hydrophobic chain architectures for atherosclerotic applications

246th National Meeting (2013)

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