Elucidating the Structural Features of a Class of PAMAM−Acyl Synthetic Lipid Nanoparticles

Abstract Herein, we characterize a class of PAMAM/acyl synthetic lipids and their self-assembled nanostructures. We explicitly determined the impact of hydrocarbon length, saturation, and synthetic lipid volume on the properties of the self-assembled, single-component nanostructure. The synthesis of the PAMAM−acyl lipid library was confirmed using nuclear magnetic resonance (1H NMR). Thermodynamic stability and morphological features of the LNPs were evaluated in the hydrated state using light and small-angle X-ray scattering, respectively. LNP structures were visualized using electron microscopy. The internal phase properties of the LNPs were determined using thermal analyses, showing thermal transitions dependent upon the molecular architecture of the individual lipid. PAMAM−acyl synthetic lipids exhibit a rich morphology of vesicles and micelles, with nanoparticle sizes, morphology, and bilayer arrangements that are determined primarily by the length of the acyl tail and size of the PAMAM head group. Finally, we interrogate model drug loading to envision future applications in drug delivery.