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

Widad Henni-Silhadi (1) , Michel Deyme (1) , Martine Boissonnade (1) , Martine Appel (1) , Didier Le Cerf (2) , Luc Picton (2) , Véronique Rosilio (1)

1 PCPB - Physico-chimie, pharmacotechnie, biopharmacie
2 PBM - Polymères, biopolymères, membranes

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.

Keywords: cytotoxicity studies; docetaxel; hydrophobically modified carboxymethylpullulan; solubilization; surface tension

Domains: Chemical Sciences; Chemical Sciences; Polymers

Widad Henni-Silhadi, Michel Deyme, Martine Boissonnade, Martine Appel, Didier Le Cerf, et al.. Enhancement of the Solubility and Efficacy of Poorly Water-Soluble Drugs by Hydrophobically-Modified Polysaccharide Derivatives. Pharmaceutical Research, 2007, 24 (12), pp.2317 - 2326. ⟨10.1007/s11095-007-9461-7⟩. ⟨hal-01866832⟩