Polyphosphoester-Based Drug Delivery Systems

Polyphosphoesters (PPEs) have emerged as a versatile class of biodegradable polymers for drug delivery, distinguished by a backbone of phosphate ester linkages. Their synthetic accessibility via ring-opening polymerisation of cyclic phosphoesters allows precise tuning of molecular weight, chain architecture and side-chain functionality. Amphiphilic PPEs spontaneously self-assemble into micelles, vesicles and other nanostructures that can encapsulate hydrophobic therapeutics, while hydrophilic PPEs function as stealth coatings to prolong circulation and reduce protein adsorption. Degradation proceeds by controlled hydrolysis and enzymatic cleavage of the phosphoester bonds, yielding non-toxic by-products. Functional handles introduced during or after polymerisation enable targeting ligands, stimuli-responsive moieties and cross-linking chemistries, supporting site-specific release and theranostic integration. Compared with traditional polyesters and poly(ethylene glycol), PPEs offer enhanced chemical diversity, predictable degradation kinetics and the possibility of direct imaging through phosphorus-sensitive modalities. Their biocompatibility and adaptable properties have catalysed advances in cancer chemotherapy, gene delivery, immunotherapy and magnetic resonance–guided interventions, underscoring the global relevance of PPE-based platforms across pharmaceutical and translational research.

Research from Nature Portfolio

Recent studies have demonstrated the preparation of amphiphilic gradient copolymers through organocatalysed ring-opening copolymerisation of cyclic phospholane monomers. By modulating reactivity ratios and comonomer feed, researchers achieved PPEs with tailored amphiphilicity and microstructure, leading to self-assembled nanostructures in aqueous media. These materials exhibit tunable interfacial properties and phosphorus-rich domains that afford intrinsic contrast in 31P magnetic resonance imaging, enabling non-invasive tracking of carrier distribution alongside cargo delivery. Such dual-function PPE nanomaterials highlight an integrated approach to combine precise polymer design with diagnostic imaging capabilities.

Polyphosphoester-Based Drug Delivery Systems publication trend

The graph below shows the total number of articles in polyphosphoester-based drug delivery systems across all publications each year (not limited to Nature Index journals).

Technical terms

Polyphosphoester (PPE): Polymer whose main chain comprises phosphate ester bonds, conferring biodegradability and chemical versatility for drug delivery.

Ring-opening polymerisation (ROP): Polymerisation method that opens cyclic monomers to form linear polymers with controlled molecular weight and architecture.

Amphiphilicity: Molecular property combining hydrophilic and hydrophobic segments, driving self-assembly into nanocarriers such as micelles.

Reactivity ratio: Parameter describing the relative incorporation tendencies of comonomers during copolymerisation, influencing gradient or block architectures.

31P MRI: Magnetic resonance imaging technique that detects phosphorus nuclei, enabling the non-invasive tracing of phosphorus-containing nanomaterials in vivo.

References

1. Real-time 31P NMR reveals different gradient strengths in polyphosphoester copolymers as potential MRI-traceable nanomaterials. Communications Chemistry (2023).
2. Functional biodegradable polymers via ring-opening polymerization of monomers without protective groups. Chemical Society Reviews (2018).
3. Main-chain water-soluble polyphosphoesters: Multi-functional polymers as degradable PEG-alternatives for biomedical applications. European Polymer Journal (2020).
4. Recent advances in degradable synthetic polymers for biomedical applications ‐ Beyond polyesters. Progress in Polymer Science (2022).