Development of Amino Acid Lipids and Liposomes for Targeted Drug Delivery

Liposomes that incorporate mechanisms for triggered release under mildly acidic conditions could deliver medicines to the hyperacidic surfaces of many tumors. Our group as been investigating the use of amino acid-derived lipids that self-assemble into nanoparticles as drug carriers for both hydrophilic and hydrophobic drugs. The asparagine-derived lipid analogue with one 11 carbon chain (ALA11) in combination with cholesterol forms nanoparticles that decompose when exposed to mildly acidic conditions. Currently, it is unknown if ALA11 could be furthered stabilized to create pH-responsive nanoparticles for targeted drug delivery. In this project, we are investigating the hypothesis that ALA11, in combination with distearoylphosphatidylcholine (DSPC) and cholesterol, can be employed to develop a stable liposome capable of pH-activated release. We synthesized the heterocyclic lipid by reacting asparagine with dodecanal under basic conditions and confirmed the structure spectroscopically. The lipids will be self-assembled into liposomes by hydrating a lipid thin film and the nanoparticles will be characterized using dynamic light scattering (DLS) and scanning electron microscopy (SEM). The development of pH-sensitive liposomes capable of triggered release could increase drug delivery to affected tissues while also resulting in fewer side effects in healthy tissue. This work was partially supported by TWD RISE GM60655 and the Department of Chemistry at the University of Texas at San Antonio.