Cytotoxicity optimal ratio

Ray and coworkers (31) studied the liver protective properties of cleomiscosins A (9), B (10) and C (7), isolated from Cleome viscosa seeds, and found significant activity against D-galactosamine-induced cytotoxicity in primary cultured rat hepa-tocytes, with 10 being the most potent of these substances. Chattopadhyay et al. (33) have patented a hepatoprotective pharmaceutical preparation (Cliv-92), composed of a mixture of three coumarinolignans isolated fi om the seeds of C. viscosa, in the optimized ratio of 3 5 2. 

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). 

---