Biomedical Applications

Polyphosphates and –phosphonates as degradable polymers for bioapplications and drug carriers

The “gold standard” for soluble polymers in biomedical applications, even after 50 years of progress, is still poly(ethylene glycol) (PEG) as a non-toxic, biocompatible, “stealth” polymer. The beneficial effect of PEGylation on the pharmacokinetics of drugs has been proven in vitro, in vivo, and in clinical applications. However, PEG is not hydrolytically degradable, leading to accumulation after repeated administration and shows a distinct lack of functionality which limits the variation of properties by chemical means. Finally, anti-PEG antibodies have been detected in patients treated with PEGylated drugs on a regular basis and healthy blood donors, leading to accelerated clearance of the drug and decreasing its pharmacological efficacy.

Synthetic poly(phosphoester)s (PPEs), a polymer class discussed as complements for PEG, are inspired by the DNA, the most essential natural PPE. DNA benefits from the unique properties of phosphorus as the PPE backbone provides stability, functional, precise synthesis, and targeted degradation. Synthetic PPEs, compared to traditional poly(carboxylic acid ester)s, provide several benefits: the pentavalent phosphorus contributes one bond per repetition unit for side-chain modifications. An additional modification of the phosphorus binding sphere gives access to an even more extensive chemical diversity (P-O, P-C, P-N, P-S). Finally, aside from the P-C bond, all P-X binding motives are hydrolytically cleavable, affording a completely biodegradable and biocompatible polymer backbone.

Our research focuses on the development of novel synthetic PPEs to be used in biomedical applications. We pursue a bottom up process starting with the monomer synthesis, followed by polymerization via different polymerization processes. In the course of these investigations we discuss fundamental questions concerning material properties, biocompatibility, degradability, and the fundamental origins of the “stealth” effect. But also from the viewpoint of applications we successfully developed, e.g., biodegradable PPE-protein conjugates and temperature-sensitive polymersomes exhibiting UCST like swelling/disassembly for drug release.

Our group is thus covering a broad field of applications and motivations, all due to the high chemical flexibility provided by poly(phosphoester)s.

Selected publications:

Wolf, T.; Rheinberger, T.; Simon, J.; Wurm, F. R.
Reversible Self-Assembly of Degradable Polymersomes with Upper Critical Solution Temperature in Water.
Soc. 2017, 139 (32), 11064-11072
Schöttler, S.; Becker, G.; Winzen, S.; Steinbach, T.; Mohr, K.; Landfester, K.; Mailänder, V.; Wurm, F. R.
Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers.
Nat Nano 2016, 11 (4), 372-377
Wolf, T.; Steinbach, T.; Wurm, F. R.
A Library of Well-Defined and Water-Soluble Poly(alkyl phosphonate)s with Adjustable Hydrolysis.
Macromolecules 2015, 48 3853–3863
Steinbach, T.; Wurm, F. R.
Poly(phosphoester)s: A new platform for degradable polymers.
Angew. Chem. Int. Ed. 2015, 54, 6098-6108
Wolf, T.; Rheinberger, T.; Wurm, F. R.
Thermoresponsive coacervate formation of random poly(phosphonate) terpolymers.
Eur. Polym. J. 2017, 95 (Supplement C), 756-765
Degradable Polyphosphoester-Protein Conjugates: “PPEylation” of Proteins.
Steinbach, T.; Wurm, F. R.
Biomacromolecules 2016, 17 (10), 3338-3346
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