Structural and Surface Properties of Polyamidoamine (PAMAM) – Fatty Acid‐based Nanoaggregates Derived from Self‐assembling Janus Dendrimers

Abstract This study summarizes the synthesis, characterization, and evaluation of a library of biocompatible self‐assembling Janus dendrimers (JDs) and their resulting nanostructures possessing either a cationic (NH₃⁺), anionic (COO⁻), or neutral (OH) surface. Strategically designed for applications in therapeutic delivery, the dendrimers are comprised of a polyamidoamine (PAMAM) dendron as the hydrophilic portion and fatty acid (FA) functionalized dendrons as the hydrophobic portion. The physicochemical characterization and in vitro cell viability of amphiphilic JDs were performed. Microscopy (TEM) and dynamic light scattering (DLS) analysis indicate the size (i. e., diameters) of spherical nanoaggregates ranging from 40 to 100 nm with zeta‐potential values ranging from −17.9 to +58.7 mV with respect to the terminal functional group of the JD employed. Furthermore, these systems exhibited spherical nanoaggregates with critical aggregate concentrations (CAC) ranging from 2.8 to 7.0 mg/L. At low concentrations (<200 μg/mL), JDs nanoaggregates showed minimal cell growth inhibitory properties in the in vitro testing, demonstrating their safety. The results of this study prove that a simple yet strategic combination of chemically distinctive dendritic segments can afford a versatile library of unique JDs nanoplatforms with excellent potential for biomedical applications.