Polyphosphazene Drug Conjugates

In recent years the chemistry of Pt complexes has progressed rapidly, for example, the development of cytotoxic Pt(IV) prodrugs, which offer numerous advantages over traditional Pt(II) complexes, has helped to overcome the problem of intrinsic and acquired drug resistance and provides a reduced systematic toxicity due to their intracellular activation [130]. As it is well known that 

Polymer backbone ---Hydrophilic side chains Targeting group Drug 

Nischang and O. Briiggemann, Polymer Chemistry, 2011, 2, 4, 828. 2011, Royal Society of Chemistry [137] 

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Enhanced blood circulation times in comparison to the free drug were unambiguously identified, with the polyphosphazene conjugate still active even after 24 h (Figure 3.19). Furthermore, a significant tumour selective uptake (tumour/tissue ratio >4) was observed, in contrast to carboplatin, presumably as a consequence of the EPR effect [125]. Further studies showed a maximum tumour/tissue ratio at 24 h for the polymer with a = 62 800 and = 11.4 nm [127], however the differences in tumour accumulation were small and did not correlate with the cytotoxicity data, hence further studies are required to determine the optimal M. The EPR effect is known to vary between tumour types [128] and furthermore, the polymer-series tested is likely to be quite polydisperse, although no values are given, due to the synthesis method used (see Chapter 1). 

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