Self-assembled micelles of monosialogangliosides as nanodelivery vehicles for taxanes

LEONHARD V; ALASINO RV; BIANCO ID; BELTRAMO DM

Potrero de los Funes, San Luis

Exposición; 47th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2011

SAIB

Background: Taxanes are anticancer agents that, due to their poor aqueous solubility, are formulated in vehicles associated with severe side effects. On the other side, gangliosides are amphipathic molecules that spontaneously self-assemble in water as micelles. Objective:  Characterization of the interactions between taxanes and ganglioside micelles (water-solubility, structure, stability, cytotoxicity). Methods: UV-Vis spectrometry, DLS, EM and chromatography were used to characterize water-solubility and structure. Human larynx hepithelioma cell cultures were used to assess cytotoxicity. Results: Water solubility of paclitaxel (Ptx) is 1 µg/mL and increases up to 7 mg/mL upon its association with GM1 micelles. The incorporation of Ptx in GM1 reaches an optimum at Ptx:GM1 1:20 molar ratio. Loading of the Ptx into the micelle induces a structural reorganization that leads to a reduction in size and an important protection of Ptx reducing its hydrolysis at alkaline pH. Diffusion of either GM1 or Ptx is restricted upon mixed-micelle formation. In vitro assays show that Ptx is incorporated by the cells and has antimytotic activity equivalent to that of free Ptx. Conclusions: Ptx is spontaneously incorporated in GM1 micelles, increasing its water solubility by at least 7,000 times. Complexes thus formed are more stable and does not affect the biological antimytotic activity of Ptx.