BIANCO ISMAEL DARÍO
Congresos y reuniones científicas
Título:
Sequetial loading of paclitaxel (PTX) and doxorubicin (D) into ganglioside micelles
Autor/es:
ALASINO R.V.; V. LEONHARD; 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: Doxorubicin (D) is an anticancer agent that has
important toxic effects and low water solubility. Gangliosides
spontaneously self-assemble in water as micelles and have been
shown to increase water solubility of Paclitaxel (Ptx).
Objective: Characterization of the interactions between Ptx, D and
ganglioside micelles (water-solubility, structure, stability,
cytotoxicity).
Methods: UV-Vis spectrometry, DLS, EM and chromatography
were used to characterize water-solubility and structure. Hep-2 and
HeLa cell cultures were used to assess cytotoxicity.
Results: GM1 micelles increase water solubility of D up to 20
mg/mL leading to a micellar structure that protects D from alkaline
hydrolysis. Similar results are obtained with Ptx:GM1 (1:20 molar
ratio) micelles. However, incorporation of D into GM1 micelles
impairs the incorporation of Ptx. Ternary micelles have greater
stability than any of the components. Micelles are reorganized upon
drug loading leading to smaller structures with a mean diameter of
10 nm. In vitro assays show that both drugs penetrate into HeLa and
Hep-2 cells and are directed to microtubules (Ptx) and the cell
nucleus (D).
Conclusions: GM1 spontaneously loads Ptx and D into different
nano-domains of stable and water soluble 10 nm micelles that
deliver the drugs to HeLa and Hep-2 cells similarly than the
respective free drugs. Co-delivery of Ptx and D enhance
chemotherapy in vitro.
important toxic effects and low water solubility. Gangliosides
spontaneously self-assemble in water as micelles and have been
shown to increase water solubility of Paclitaxel (Ptx).
Objective: Characterization of the interactions between Ptx, D and
ganglioside micelles (water-solubility, structure, stability,
cytotoxicity).
Methods: UV-Vis spectrometry, DLS, EM and chromatography
were used to characterize water-solubility and structure. Hep-2 and
HeLa cell cultures were used to assess cytotoxicity.
Results: GM1 micelles increase water solubility of D up to 20
mg/mL leading to a micellar structure that protects D from alkaline
hydrolysis. Similar results are obtained with Ptx:GM1 (1:20 molar
ratio) micelles. However, incorporation of D into GM1 micelles
impairs the incorporation of Ptx. Ternary micelles have greater
stability than any of the components. Micelles are reorganized upon
drug loading leading to smaller structures with a mean diameter of
10 nm. In vitro assays show that both drugs penetrate into HeLa and
Hep-2 cells and are directed to microtubules (Ptx) and the cell
nucleus (D).
Conclusions: GM1 spontaneously loads Ptx and D into different
nano-domains of stable and water soluble 10 nm micelles that
deliver the drugs to HeLa and Hep-2 cells similarly than the
respective free drugs. Co-delivery of Ptx and D enhance
chemotherapy in vitro.
