Marie-Martine Boissonnade

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

PurposeThis 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.MethodsThe 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.ResultsCompared 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.ConclusionsCMP49C8 is a good candidate for solubilizing hydrophobic drugs and could be applied to docetaxel formulations.

Adsorption of glucose oxidase into lipid monolayers: effect of a lipid headgroup charge

The effect of both lipid headgroup charge and of aqueous subphase pH on adsorption of glucose oxidase molecules (GOx) into dibehenoylphosphatidylcholine (DBPC) and octadecylamine (ODA) monolayers has been studied by surface tension and surface pressure measurements. The results revealed that whereas the extent of GOx adsorption into pure DBPC monolayers essentially depended on the area in a monolayer available to harbor adsorbing GOx molecules, enhanced enzyme penetration into a monolayer occurred at high surface densities. The kinetics of enzyme penetration was found to be dependent of the initial surface pressure of a spread monolayer. The addition of ODA to DBPC monolayers gave a dramatic boost to GOx penetration and at high molecular surface densities largely depended on the ratio of ODA in the mixed monolayers. This increase in GOx penetration was attributed to the strong attractive electrostatic interaction between the positively charged ODA and the negatively charged enzyme.

Cratylia mollis lectin at the air–aqueous solution interface: adsorption and lectin–lipid interactions

The interfacial behaviour of Cratylia mollis (Cra) at the air/water interface and its penetrant ability into spread phospholipid monolayers (Lipoid E80 and Epicuron 200) has been monitored by surface tension measurements. The first-order rate constants defining adsorption and rearrangement obtained from surface tension kinetics data reveal that Cra is a rather stable protein which exhibits characteristic protein adsorption patterns in which the breaking points separating diffusion–penetration and rearrangement profiles could have been easily distinguished. The penetration of Cra into Lipoid E80 and Epicuron 200 phospholipid monolayers has been inferred in terms of penetration pressure increments (ΔΠ) versus time relationships. The data clearly showed that penetrant ability of the lectin was, to a large extent, dependent on monolayer compressibilities. Thus, for Lipoid E80, which contained a rather high percentage of phosphatidylethanolamine (DPPE) in the mixture with phosphatidylcholine (DPPC), penetration of Cra at the high monolayer compression (20 mN m−1) was lower than that observed for Epicuron 200, which did not contain DPPE. Indeed, in the middle of the Π-A isotherm, DPPE was markedly less compressible than DPPC. However, at the low monolayer surface coverage (3 mN m−1), the rates of Cra penetration into both Lipoid E80 and Epicuron 200, although much higher for the latter at the beginning of adsorption, yielded similar limiting values of ΔΠ. This has been attributed to the occurrence of a hydrophobic interaction between the lectin and hydrophobic phospholipid chains that have the same length for both Lipoid E80 and Epicuron 200.

Polymer interface analysis by ESR spectra of Mn(II)

Abstract Carbonyl groups were formed on the surface of low-density polyethylene by chemical oxidation. The treated surfaces were studied by scanning electron microscopy, ATR, IR spectroscopy, and 45Ca2+ adsorption. Paramagnetic probe ions Mn(II) were adsorbed and the ESR spectra obtained for various surface compositions and thermal treatments of polyethylene. The results obtained show that ESR spectroscopy may become a promising, nondestructive method of analysis of solid polymer interfaces.