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Article Dans Une Revue International Journal of Pharmaceutics Année : 2012

Drug solubilization and in vitro toxicity evaluation of lipoamino acid surfactants

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

Résumé

To improve solubilization of a water insoluble anticancer drug, novel surfactants were synthesized. All surfactants derived from lysine, with a so-called nitrilo triacetic acid (NTA) polar head, and differed from the length and saturation degree of their hydrophobic moieties: C19:0-NTA, C20:4-NTA, C25:0-NTA and C25:4-NTA. Self-assembling properties and critical micellar concentration (CMC) values were determined using pyrene fluorescence and cytotoxicity using MTT and LDH assays on endothelial cells. Surfactant haemolytic activity and drug solubilization capacity were also evaluated. All surfactants self-assemble with low CMC values from 0.012 to 0.430 mg/mL. Cytotoxicity assays showed that C20:4-NTA and C25:0-NTA were less cytotoxic than polysorbate 80. Unsaturations and alkane chain length have a marked influence on toxicity. Saturated surfactants had a similar haemolytic activity, explained by their low CMC values and the linear configuration of their hydrophobic tail. C20:4-NTA and C25:4-NTA were less haemolytic than polysorbate 80. Furthermore, C19:0-NTA, C25:0-NTA and C25:4-NTA increased drug solubility from < 0.15 µg/mL up to 7 mg/mL, with 46 % (w/w) drug loading, due to their linear and flexible hydrophobic chain configuration, as evidenced by molecular modeling. Although these solubilizers are promising, a compromise between drug solubilisation and toxicity remains to be found.
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Dates et versions

hal-04101335 , version 1 (19-05-2023)

Identifiants

Citer

Nathalie Ménard, Nicolas Tsapis, Cécile Poirier, Thomas Arnauld, Laurence Moine, et al.. Drug solubilization and in vitro toxicity evaluation of lipoamino acid surfactants. International Journal of Pharmaceutics, 2012, 423 (2), pp.312-320. ⟨10.1016/j.ijpharm.2011.11.030⟩. ⟨hal-04101335⟩
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