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Enhancement of the solubility and efficacy of poorly water-soluble drugs by hydrophobically-modified polysaccharide derivatives.

Henni-Silhadi W, Deyme M, Boissonnade MM, Appel M, Le Cerf D, Picton L, Rosilio V

Physico-Chimie des Surfaces Univ Paris-Sud, UMR CNRS 8612, 5 Rue Jean-Baptiste Clément, 92296, Châtenay-Malabry Cedex, France.

PURPOSE: This work was intended to develop and evaluate a new polymeric system based on amphiphilic carboxymethylpullulans (CMP(49)C(8) and CMP(12)C(8)) that can spontaneously self-assemble in aqueous solutions and efficiently solubilize hydrophobic drugs. METHODS: The self-assembling properties of CMP(49)C(8) and CMP(12)C(8) 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 CMP(49)C(8) solutions and the docetaxel commercial vehicle (Tween 80/Ethanol-water) were evaluated in the absence and in the presence of docetaxel. RESULTS: Compared to CMP(12)C(8), CMP(49)C(8) 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 CMP(49)C(8) 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 CMP(49)C(8)-docetaxel formulation was equipotent to the commercial docetaxel one. Furthermore, in the absence of the drug, CMP(49)C(8) appeared less cytotoxic against macrophages than the Tween 80/Ethanol-water. CONCLUSIONS: CMP(49)C(8) is a good candidate for solubilizing hydrophobic drugs and could be applied to docetaxel formulations.

Published 6 November 2007 in Pharm Res, 24(12): 2317-26.
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