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Article Dans Une Revue Pharmaceutical Research Année : 2012

Novel surfactants with diglutamic acid polar head group: drug solubilization and toxicity studies

Nathalie Ménard
  • Fonction : Auteur
Cécile Poirier
  • Fonction : Auteur
Thomas Arnauld
  • Fonction : Auteur
Laurence Moine
  • Fonction : Auteur
Claire Gignoux
  • Fonction : Auteur
François Lefoulon
  • Fonction : Auteur
Jean-Manuel Péan
  • Fonction : Auteur
Elias Fattal

Résumé

Purpose Novel surfactants made of diglutamic acid (DG) polar head linked to lithocholic, arachidonic, linoleic or stearic acids were designed for drug solubilization. Methods Surfactants 3-D conformer and packing parameter were determined by molecular modelling and self-assembling properties by pyrene fluorescence measurements. Cytotoxicity was assessed on Human Umbilical Vein Endothelial Cells (HUVEC) and haemolyitic activity on rat red blood cells. Drug solubilization was quantified and its interaction with hydrophobic moieties were characterized using differential scanning calorimetry and X-ray diffraction. Self organisation of stearoyl-DG was observed by cryogenic transmission electron microscopy. Toxicity after repeated injections of stearoyl-DG was investigated in Wistar rats. Results DG-based surfactants self-assemble into water and their critical micellar concentration are comprised between 200 and 920 µg/mL. Cytotoxicity and haemolysis were lower than for polysorbate 80. At best, stearoyl-DG solubilized the drug up to 22 % (w/w). Solid-state characterization evidenced drug/lipid interactions leading to the formation of a new complex. Stearoyl-DG formed spherical micelles of 20 nm, as predicted by packing parameter calculation. However, it induced a possible liver toxicity after intravenous administration in rats. Conclusions Among the surfactants tested, stearoyl-DG is the more efficient for drug solubilization but its use is limited by its possible liver toxicity.
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Dates et versions

hal-04101338 , version 1 (19-05-2023)

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Nathalie Ménard, Nicolas Tsapis, Cécile Poirier, Thomas Arnauld, Laurence Moine, et al.. Novel surfactants with diglutamic acid polar head group: drug solubilization and toxicity studies. Pharmaceutical Research, 2012, 29 (7), pp.1882-1896. ⟨10.1007/s11095-012-0714-8⟩. ⟨hal-04101338⟩
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