Water‐soluble, biocompatible polyphosphazenes with controllable and pH‐promoted degradation behavior

Abstract

The synthesis of a series of novel, water-soluble poly(organophosphazenes) prepared via living cationic polymerization is presented. The degradation profiles of the polyphosphazenes prepared are analyzed by GPC, 31P NMR spectroscopy, and UV–Vis spectroscopy in aqueous media and show tunable degradation rates ranging from days to months, adjusted by subtle changes to the chemical structure of the polyphosphazene. Furthermore, it is observed that these polymers demonstrate a pH-promoted hydrolytic degradation behavior, with a remarkably faster rate of degradation at lower pH values. These degradable, water soluble polymers with controlled molecular weights and structures could be of significant interest for use in aqueous biomedical applications, such as polymer therapeutics, in which biological clearance is a requirement and in this context cell viability tests are described which show the non-toxic nature of the polymers as well as their degradation intermediates and products.

Chain‐End‐Functionalized Polyphosphazenes via a One‐Pot Phosphine‐Mediated Living Polymerization

“…Poly(organo)phosphazenes are an extremely versatile class of hybrid inorganic–organic polymers whose properties and functionality can be easily tuned by suitable organic side groups attached to the inorganic backbone, [1] and thus can be used to prepare a wide-array of interesting materials, ranging from superhydrophobic polymers [2] and high-performance elastomers, [3] to thermoresponsive polymers [4] and biodegradable polymers [5] for a multitude of biomedical applications, [6] such as tissue engineering [7] and advanced drug delivery systems. [8] …”

Branched Macromolecular Architectures for Degradable, Multifunctional Phosphorus‐Based Polymers

“…Furthermore, introducing hydrolysis sensitizing amino acid esters as co‐substituents represents a simple route to fine tune degradation rates . Amino acid units have also been shown to sensitize polyphosphazenes towards hydrolysis when used as spacers between the phosphorus and the organic substituents, that is replacing the ethyl ester with for example allyl groups for photochemical cross‐linking or water solubilizing groups (Figure ) . Extension of the amino acid unit to short peptides can also be used to tune degradation profiles.…”

“…This has been shown to lead to an enzymatically triggered degradation, whereby cleavage of the peptide exposes the phosphazene backbone to hydrolysis and thus an accelerated degradation profile is observed in the presence of the enzyme . Degradation studies carried out at different pH values show a much faster decrease in molecular weight at acidic pH values compared to neutral pH for many different polyphosphazenes whilst interestingly, in contrast to e.g., polyphosphoesters (vide infra), slower degradation kinetics are observed under basic conditions . The degradation kinetics of the cyclic phosphazene trimer, and hence polymers based thereon, have been less widely investigated, although have been shown in principle also to hydrolyze with a ring‐opening to phosphates and ammonium …”

Photopolymerizable Porous Polyorganophosphazenes

“…Therefore, Polymer 5 is more hydrophilic and should degrade faster than for instance Polymer 3 [111]. The considerable improvement achieved by this polymer is, that it contains a combination of an amino acid and a double bond donor.…”

“…The mixed Polymer 8 contained a glycine ester and an ethylene glycol allyl ether to fulfill the requirement of a hydrophilic and fast degrading polymer via the glycine ester [111] and a non-toxic double bond donor via the ethylene glycol allyl ether. The significant disadvantage of mixed polymers is that it is impossible to repeat the exact ratio of the two side chains.…”