Design, synthesis, and characterization of next generation lipid nanoparticles

Lipid nanoparticles (LNPs) have emerged in the literature as a viable vehicle for therapeutic delivery, gaining significant popularity over the last 30 years. LNPs are composed of a mixture of biocompatible lipids, which results in variance in nanoparticle properties such as size, surface charge density, or rigidity. This heterogeneity within the formulation can decrease targeting efficiency in drug delivery applications. To address these challenges, we have developed a library of structurally tunable lipid nanoparticles (stLNPs) formed by the self-assembly of a single synthetic lipid with modifiable features. This results in uniform physical (i.e. size and morphology) and mechanical (i.e. rigidity, flexibility, and bilayer morphology) properties across the nanoparticle formulation and allows for the specific selection of LNP properties ideal for the application. With a long-term goal of advancing these materials towards clinical application for targeted transdermal delivery, we have designed and characterized synthetic lipids comprised of a poly amidoamine (PAMAM) dendron chemically linked to an acyl tail group. We have incorporated tunable features that afford nanoparticles with a range of properties.