Sequential loading of paclitaxel (Ptx) and Doxorubicin (D) into ganglioside micelles

ALASINO RV; LEONHARD V; BIANCO ID; BELTRAMO DM

Potrero de los Funes, San Luis

Exposición; 47 Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011

SAIB

Background: 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 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.