Main-Chain Phosphorus-Containing Polymers for Therapeutic Applications

Abstract

Polymers in which phosphorus is an integral part of the main chain, including polyphosphazenes and polyphosphoesters, have been widely investigated in recent years for their potential in a number of therapeutic applications. Phosphorus, as the central feature of these polymers, endears the chemical functionalization, and in some cases (bio)degradability, to facilitate their use in such therapeutic formulations. Recent advances in the synthetic polymer chemistry have allowed for controlled synthesis methods in order to prepare the complex macromolecular structures required, alongside the control and reproducibility desired for such medical applications. While the main polymer families described herein, polyphosphazenes and polyphosphoesters and their analogues, as well as phosphorus-based dendrimers, have hitherto predominantly been investigated in isolation from one another, this review aims to highlight and bring together some of this research. In doing so, the focus is placed on the essential, and often mutual, design features and structure–property relationships that allow the preparation of such functional materials. The first part of the review details the relevant features of phosphorus-containing polymers in respect to their use in therapeutic applications, while the second part highlights some recent and innovative applications, offering insights into the most state-of-the-art research on phosphorus-based polymers in a therapeutic context.

Intracellular Delivery of Active Proteins by Polyphosphazene Polymers

“…The polymers used in this study were (a) PZs containing 70% (mol) carboxylic acid and 30% (mol) pyrrolidone side groups, i.e., poly[(carboxylatoethylphenoxy)(3-(2-oxo-1pyrrolidinyl)propylamino)phosphazene], herein called PZ-PYR, or (b) PZ containing 84% (mol) carboxylic acid and 16% (mol) graft 5 kDa polyethylene glycol (PEG) side groups, i.e., poly[di(carboxylatoethylphenoxy)phosphazene]-graft-poly(ethylene glycol), herein called PZ-PEG ( Figure 1A). They were synthesized via macromolecular substitution route as described previously [28,29,34]. PZ-PYR or PZ-PEG solutions were then vortexed for 2 min and mixed at 0.6 mg/mL polymer and 0.3 mg/mL protein cargos, including FITC-labeled avidin as a model protein, anti F-actin antibody, or Bax-BH3 peptide as active cargos.…”

Biomedical applications of polyphosphazenes

“…Hence, polyphosphazenes can possess immobilization capabilities and tend to degrade to release the immobilized molecules, which can have therapeutic effects (Figure 2; Ni et al, 2020;Ogueri et al, 2020a;Strasser & Teasdale, 2020).…”

“…One of the most intriguing parts of macromolecular substitution reaction is its variability that allows the incorporation of several biologically relevant groups onto the skeletal backbone of polyphosphazenes (Ogueri et al, 2020a). Hence, polyphosphazenes can possess immobilization capabilities and tend to degrade to release the immobilized molecules, which can have therapeutic effects (Figure 2; Ni et al, 2020; Ogueri et al, 2020a; Strasser & Teasdale, 2020).…”

“…Thus, polyphosphazenes provide a versatile tool that can manage this trade‐off, and they offer an optimal biologic interface between the surface of medical implants and native tissues (Z. Huang et al, 2018; Ogueri, Ogueri, Allcock, & Laurencin, 2020a; Potta, Chun, & Song, 2010). Polyphosphazene‐based polymers are a class of inorganic–organic hybrid polymers with an unusual polymer skeletal backbone composed of alternating phosphorous and nitrogen atoms (Ogueri, Allcock, & Laurencin, 2019; Strasser & Teasdale, 2020). Each phosphorous atom is linked with two substituents (e.g.…”

“…The ones with substituents such as amino acid esters and peptide esters constitute the largest group of degradable polyphosphazenes and have been extensively investigated and developed as tissue constructs for bone regenerative engineering (Allcock & Morozowich, 2012; Ogueri & Laurencin, 2018). Also, degradable polyphosphazenes have shown promise in their applications as carriers for the controlled release of bioactive and therapeutic molecules (Ogueri et al, 2020a; Salinas et al, 2020; Strasser & Teasdale, 2020). The process of tissue regeneration and the release of immobilized molecules can be controlled and regulated by modulating the degradation of polyphosphazenes (Ni et al, 2020; Ogueri, Allcock, et al, 2019; Ogueri et al, 2020a).…”