BIANCO ISMAEL DARÍO
Congresos y reuniones científicas
Título:
Self-assembled ganglioside micelles as nanodelivery vehicles of taxanes
Autor/es:
V. LEONHARD; ALASINO R.V.; BIANCO I.D.; BELTRAMO D.M.
Lugar:
Potrero de los Funes, San Luis
Reunión:
Congreso; 47th Annual Meeting Argentine Society for Biochemistry and Molecular Biology (XLVII Reunión annual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011
Institución organizadora:
SOCIEDAD ARGENTINA DE INVESTIGACIN EN BIOQUIMICA Y BIOLOGIA MOLECULAR
Resumen:
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 do not affect the biological
antimytotic activity of Ptx.
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 do not affect the biological
antimytotic activity of Ptx.
