Multifunctional and biodegradable polyphosphazenes for use as macromolecular anti-cancer drug carriers

Using a living cationic polymerisation procedure we synthesised a series of multi-armed poly(organo)phosphazenes with controlled molecular weights and excellent aqueous solubility. The synthetic flexibility of polyphosphazenes was exploited in order to incorporate an acid-sensitive hydrazide linker to the polymer backbone, as well as tumour-targeting folic acid groups. We were then able to attach hydrophobic anti-cancer drug molecules via the pH labile linker and studied its pH-triggered release kinetics from the polymeric carrier. Although stable for short periods (several days) in an aqueous environment, the polymers were shown to degrade over longer periods (weeks) under simulated physiological conditions. Furthermore, the rate of degradation could be tailored through careful selection of substituents. These biodegradable, multi-functional polyphosphazenes represent promising candidates for use as macromolecular carriers for the tumour-targeted delivery of anti-cancer drugs.