Intrinsic acetamide brush-off by polyurea biodendrimers

Area of Science:

• Pharmaceutical Nanotechnology
• Drug Safety and Impurity Profiling
• Polymer Science

Background:

• Genotoxic impurities, such as acetamide, pose significant risks in active pharmaceutical ingredients (APIs) manufacturing.
• Current methods for scavenging acetamide, a common byproduct of acetonitrile hydrolysis, remain challenging.
• Ensuring API safety necessitates effective strategies to mitigate the presence of such harmful impurities.

Purpose of the Study:

• To evaluate polyurea (PURE) biodendrimers as nanopolymers for creating safe drug nanoformulations.
• To demonstrate the selective scavenging of acetamide from drug mixtures using PURE biodendrimers.
• To utilize (S)-ibuprofen as a model drug to validate the efficacy of PURE biodendrimers.

Main Methods:

• Preparation and characterization of polyurea (PURE) biodendrimer-based nanoformulations.
• In vitro assessment of acetamide scavenging efficiency in the presence of (S)-ibuprofen.
• Computational molecular dynamics (MD) simulations to elucidate intermolecular interactions within the nanoformulations.

Main Results:

• PURE biodendrimers successfully formed safe nanoformulations from mixtures containing acetamide and (S)-ibuprofen.
• MD simulations confirmed that acetamide and drug interactions with PURE biodendrimers occur primarily at the nanoparticle surface.
• Key interactions driving PURE nanoformulation stability include hydrogen bonding, electrostatic forces, and hydrophobic interactions.

Conclusions:

• Polyurea (PURE) biodendrimers represent a promising nanopolymer strategy for the development of safe pharmaceutical formulations.
• These biodendrimers effectively scavenge genotoxic acetamide, enhancing drug safety.
• The findings are supported by both experimental data and molecular dynamics simulations, highlighting the potential of PURE biodendrimers in pharmaceutical applications.