Endotoxin sensitization with polymer

Table VII. Effect of Endotoxin Sensitization With Polymer Mole-...

The toxicity of polycarboxylic acid polymers is more sensitive to polymer structure and molecular weight than antitumor activity. The acute toxicity is markedly decreased with decreasing molecular weight (Table VI and XI). Further,polyanion polymers have been shown to highly sensitize mice to bacterial endotoxin (39)> this activity is strikingly molecular weight dependent as shown in Tables VII and XI as well as dose dependent ( 3. The enhanced sensitivity to endotoxin by synthetic anionic polymers has been extensively studied, but the mechanism of action is still not understood (39)-... 

Similar to previous studies, it was shown that as the molecular weight of the polymer fraction decreased, so did the acute toxicity (Table III). Endotoxin sensitization showed a dependence on molecular weight distribution particularly with the more active polymers such as pyran and PAAMA. 

These studies suggest that (a) the biological toxicity of polyanions increases with molecular weight (significant toxicity increases occur above 15,000 MW and becomes serious over 50,000 MW) (b) antitumor activity does not appear to be molecular weight dependent (c) antiviral activity is related to molecular weight (it is diminished below 50,000 MW) and (d) sensitization to bacterial endotoxin is related to molecular weight in the case of pyran and seems to be affected by polydispersity of the polyanionic polymer. 

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