Synthesis drug cytotoxicity determination

Mechanism of Action. The exact mechanism of action of metronidazole is not known. It is believed that this drug is reduced chemically within the parasitic cell to a metabolite that impairs nucleic acid and DNA synthesis.32 The exact nature of this metabolite, however, and other features of the cytotoxic effects of this drug remain to be determined. 

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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