Intrinsic acetamide brush-off by polyurea biodendrimers

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 challeng...

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Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2021-04, Vol.9 (15), p.3371-3376
Main Authors: Martinho, Nuno, Pires, Rita F, Zloh, Mire, Bonifácio, Vasco D. B
Format: Article
Language:English
Subjects:
Acetonitrile
Computer applications
Electrostatic properties
Genotoxicity
Hydrogen bonding
Hydrophobicity
Ibuprofen
Impurities
Molecular dynamics
Pharmaceutical industry
Pharmaceuticals
Polyureas
Scavenging
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Summary: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. Polyurea biodendrimers display an intrinsic affinity-repulsion ability towards drug-acetamide mixtures, turning these nanocarriers into an attractive platform for API purification and/or preparation of genotoxin-free nanoformulations.
ISSN:2050-750X
2050-7518
DOI:10.1039/d1tb00105a