The presence of genotoxic impurities in active pharmaceutical ingredients (APIs) is a major concern for the pharmaceutical industry. Acetamide is a common genotoxic byproduct found in synthetic routes of many APIs, mainly due to acetonitrile hydrolysis, and selective scavenging is a still a challenging task. Herein, as a proof-of-concept, we evaluate polyurea (PURE) biodendrimers as strategic nanopolymers to prepare safe drug nanoformulations from mixtures containing acetamide, using (S)-ibuprofen (IBF) as a model drug. Furthermore, computational molecular dynamics (MD) simulations were conducted to rationalize in vitro results and to identify the key intermolecular interactions within mixtures. Experimental data were corroborated by MD simulations which showed that acetamide, IBF and carboxyfluorescein interactions with PURE biodendrimers are mostly at the surface. Also, PURE nanoformulations appear to be driven by hydrogen bonding, electrostatic and hydrophobic interactions.