Enhancement of the Solubility and Efficacy of Poorly Water-Soluble Drugs by Hydrophobically-Modified Polysaccharide Derivatives

Purpose This work was intended to develop and evaluate a new polymeric system based on amphiphilic carboxymethylpullulans (CMP₄₉C₈ and CMP₁₂C₈) that can spontaneously self-assemble in aqueous solutions and efficiently solubilize hydrophobic drugs. Methods The self-assembling properties of CMP₄₉C₈ and CMP₁₂C₈ were characterized by fluorescence spectroscopy and surface tension measurements. The solubilization of benzophenone and docetaxel was assessed from surface tension measurements, UV spectrometry and HPLC assays. The in vitro cytoxicity of CMP₄₉C₈ solutions and the docetaxel commercial vehicle (Tween 80?/Ethanol–water) were evaluated in the absence and in the presence of docetaxel. Results Compared to CMP₁₂C₈, CMP₄₉C₈ in aqueous solutions appeared to self-organize into monomolecular aggregates containing hydrophobic nanodomains, and to significantly increase the apparent solubility of benzophenone. Docetaxel solubility could also be improved in the presence of CMP₄₉C₈ but to a lower extent due to the surface properties of the drug. Nevertheless, in vitro, the cytotoxicity studies revealed that against cancer cells, the CMP₄₉C₈-docetaxel formulation was equipotent to the commercial docetaxel one. Furthermore, in the absence of the drug, CMP₄₉C₈ appeared less cytotoxic against macrophages than the Tween? 80/Ethanol–water. Conclusions CMP₄₉C₈ is a good candidate for solubilizing hydrophobic drugs and could be applied to docetaxel formulations.