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

被引:43
作者
Henni-Silhadi, Widad
Deyme, Michel
Boissonnade, Marie-Martine
Appel, Martine
Le Cerf, Didier
Picton, Luc
Rosilio, Veronique
机构
[1] Univ Paris Sud, UMR Physicochim Surfaces 8612, CNRS, F-92296 Chatenay Malabry, France
[2] Univ Paris Sud, UMR Culture Cellulaire 8612, CNRS, F-92296 Chatenay Malabry, France
[3] Univ Rouen, CNRS, UMR Polymeres Biopolymeres Membranes 6522, F-76821 Mont St Aignan, France
关键词
cytotoxicity studies; docetaxel; hydrophobically modified carboxymethylpullulan; solubilization; surface tension;
D O I
10.1007/s11095-007-9461-7
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 (R)/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 (R) 80/Ethanol-water. Conclusions. CMP49C8 is a good candidate for solubilizing hydrophobic drugs and could be applied to docetaxel formulations.
引用
收藏
页码:2317 / 2326
页数:10
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