Background: During the last decade, polyurethanes and polyureas have emerged as promising
alternatives to classical polyacrylate-, polyester- and polyaminoacid-based drug delivery nanosystems.
They are not only biocompatible and biodegradable, but also facilitate the manufacture of polymeric
nanostructured nanoparticles in quantitative yields. The versatile chemistry reduces the amount of
organic solvents used and allows the straightforward multifunctionalization of polymer precursors with
the desired targeting molecule at each stage of the process.
Objectives: To highlight the common issues encountered in current drug delivery systems (DDSs) and
the state of the art of polyurethane and polyurea polymers that self-assemble in a stratified manner by
hydrophobic interactions. Finally, we discuss the importance of taking a holistic view when applying
polymer nanotechnologies, in order to enhance their efficiency during preclinical and clinical studies.
Conclusions: Polyurethane-polyurea nanoparticles (PUUa NPs) emerge as suitable platforms to be
manufactured in a cost-effective manner at industrial scale and following environmentally friendly synthetic
methods. Furthermore, they allow the controlled delivery of a wide range of drugs and can be
rapidly adapted to many clinical requirements by means of FDA-approved precursors. Additionally, the
ease with which PUUa nanoparticles are biodegraded ensures control over temporal aspects of drug
delivery compared to other nanosystems. These advantages make PUUa NPs attractive drug delivery
vehicles as long as adequate safety and ethical guidelines for new NP formulations are developed.