ENHANCEMENT OF ANTI-TUMOUR ACTIVITY OF OLEYL ALCOHOL BY COMPLEXATION IN MODIFIED POLYVINYLALCOHOL POLYMER MICELLES.

The anti-tumour activity of fatty acids has been extensively investigated upon a wide range of tumour cell lines. The fatty alcohols activity, on the contrary, has been scarcely studied. It has been reported that the alcohols are more active than the corresponding acids and that unsaturated fatty alcohols inhibits DNA synthesis and growth of Erlich ascites tumour cells more efficiently than their saturated analogs. The interest in oleyl alcohol arises from dietary effects of essential fatty acids and alcohols and their involvement in cardiovascular disorders and cancers. Moreover, oleyl alcohol (cis-9-octadecen-1-ol) was reported to be one of the most active among a series of saturated and unsaturated fatty alcohols and the presence of a single insaturation makes it more stable to oxidation than multiple unsaturations. Since activity is proportionally correlated to the fatty alcohol intracellular accumulation, which depends on the balance of their hydrophobic/ hydrophilic properties and, primarily, on their ability to be solubilized in aqueous media, in this work we evaluate the possibility to improve oleyl alcohol aqueous solubilization by complexation with non toxic amphiphilic polymers self-assembling in aqueous environment. The aim is to develop safe parenteral formulations holding oleyl alcohol solubilization levels suitable to elicit therapeutic responses. The amphiphilic polymers were prepared by partial substitution of polyvinyl alcohol with oleyl chains through a succinyl spacer, in the hypothesis, previously demonstrated in an almost similar situation concerning doxorubicin [1, 2], that structural similarities should improve mutual affinity between the solubilizer and the solubilizing agent