Poly(2-oxazoline)s: the versatile polymer platform
Poly(2-oxazoline)s (commonly abbreviated as PAOx, POx, POXA or POZ) are an extraordinary polymer platform with unparalleled tunable properties and versatility. Poly(2-oxazoline)s allow a high degree of functionalization while the properties of the polymer can be accurately tuned by modifying the polymer side-chains. Poly(2-oxazoline)s are also biocompatible, and as such constitute an ideal platform for biomedicine.
The living cationic ring-opening polymerization of 2-oxazolines enables the synthesis of a wide range of polymer architectures with a variety of end-groups. The versatility of this living polymerization method allows the preparation of well-defined polyamides with tunable properties.
The hydrophilicity, hydrophobicity, stimuli-responsiveness, as well as the macroscopic behavior of the final material can be adjusted by simply varying the 2-substituent of the monomer.
- Facile introduction of functionalities in both polymer chain-ends and along the polymer side-chains.
- Living Polymerization: Straightforward access to block copolymers by sequential monomer feeding.
- Highly defined and narrow molar mass distribution.
- Accurate control over the polymer physico-chemical properties.
- Pseudo-polypeptide structure: stealth behavior, biocompatible.
- Ideal platform for biomedical applications.
Hydrophilicity – Poly(2-oxazoline)s hydrophilic/hydrophobic balance can be finely tuned.
- From more hydrophilic than poly(ethylene glycol) (PEG) via thermoresponsive to hydrophobic
- By varying the polymer composition, the transition temperature can be selected between 0 and 100 °C.
- Ideal platform to develop smart materials.
Control over the polymer thermal properties
- Amorphous and crystalline polymers.
- Tg = 80 °C (PMeOx) to -10 °C (PnHexOx).
- Ideal properties for applications in formulation, tissue-engineering, drug delivery or separation technologies.
Biodistribution studies with radiolabeled 5 kDa PMeOx and PEtOx have demonstrated rapid blood clearance (mostly after the first renal passage) and remarkably low uptake in the organs of the reticuloendotheliary system. Circulation times could be controlled by tuning the polymer chain length with no accumulation of polymers with molar mass below 40 kDa.
- Poly(2-oxazoline)s are biocompatible and non immunogenic.
- Stealth behavior: Poly(2-oxazoline)s are not recognized by the immune system.
- The polymer residence time can be controlled by the chain length.
- First PAOx/POZ therapeutic in Phase-I clinical trials.
- Poly(2-oxazoline)s are being investigated in many areas including: Half-life extension of biologicals, stability and solubility improvement, immunogenicity prevention, targeted drug release, antibody-drug conjugates (ADCs), subcutaneous drug depots for sustained release, etc.
The ULTROXA® technology
- Total control over the polymer hydrophilicity, length, and number of functionalities.
- Side-chain functionality tailored to your API.
- Tailored linkers: stable or biodegradable with controlled degradation kinetics.
- Enables high drug payload for advanced drug delivery systems (sustained, targeted) including next generation ADCs.
- Optimal platform for cross-linked hydrogels of interest in regenerative medicine or medical devices.
Our technology is already the basis of highly effective hemostats and a general adhesive tissue tape: a disruptive new medical device by GATT Technologies.
Highly defined, high molar mass poly(2-oxazoline) synthesis has been, until recently, believed to be unattainable. We have developed proprietary methods to obtain these ultra-defined polymers that enable the introduction of high molar mass poly(2-oxazoline)s in biomedicine.
Linear polyethylene imine (L-PEI) has found widespread use in gene delivery, particularly as it overcomes the cytotoxicity issues related to the use of its branched counterpart, regarded as the gold standard in gene transfection.
L-PEI is synthesized by hydrolysis of poly(2-oxazoline)s. We have strong expertise producing high-quality linear PEI and also patially hydrolized derivatives for applications spanning gene delivery to antimicrobial coatings.
Some of the ULTROXA® L-PEI features:
- Introduction of functionality (azide, alkyne, allyl, primary amine…) at the polymer chain ends.
- Optimized polymer chain length for transfection.
- Absolute control over the degree of hydrolysis for PAOx-PEI/POZ-PEI copolymers.
- Ultra-defined polymers (Đ < 1.1).
We have put together a selection of scientific publications and references so you can explore further into the fascinating field of poly(2-oxazoline)s.
General Reviews on poly(2-oxazoline)s
- K. Aoi, M. Okada, Prog. Polym. Sci. 1996.
- R. Hoogenboom, Eur. Polym. J. Special Issue. 2017.
- B. Verbraeken, K. Lava, B. Monnery, R. Hoogenboom, Eur. Polym. J. 2016.
- H. Schlaad, R. Hoogenboom, Macromol. Rapid Commun. Special Issue. 2012.
- O. Sedlacek, R. Hoogenboom, M. Hruby, et al. Macromol. Rapid Commun. 2012.
- V. R. de la Rosa, J. Mater. Sci. Mater. Med. 2013.
Poly(2-oxazoline)s Tunable Properties
- P. Goddard, J. Brookman, et al. J. Control. Release. 1989.
- T. X. Viegas, M. D. Bentley, et al. Bioconjugate Chem. 2011.
- F. C. Gaertner, R. Luxenhofer, et al. J. Control. Release. 2007.
- C. H. Wang, Y.-S. Hwang, et al. Biomacromolecules. 2011.
- M. Glassner, L. Palmieri, R. Hoogenboom, et al. Biomacromolecules. 2017.
- R. W. Moreadith, T. X. Viegas, et al. Eur. Polym. J. 2017.
- M. Glassner, L. Wyffels, R. Hoogenboom, et al. J. Control. Release. 2016.
ULTROXA® Ultra-functional Poly(2-oxazoline)s
- O. Sedlacek, R. Hoogenboom, M. Hruby, et al. Biomaterials. 2017.
- M. A. Mees and R. Hoogenboom. Macromolecules. 2015.
- M. A. Boerman, J. C. M. Van Hest, et al. J. Polym. Sci. A Polym. Chem. 2015.
- R. Hoogenboom. WO2013103297 A1. 2013..
- K. Kempe, R. Hoogenboom. M. Jaeger and U. S. Schubert. Macromolecules. 2011.
- B. Guillerm, V. Lapinte, J-J. Robin et al. Macromol. Rapid Commun. 2012.