Sequetial loading of paclitaxel (PTX) and doxorubicin (D) into ganglioside micelles

ALASINO R.V.; V. LEONHARD; BIANCO I.D.; BELTRAMO D.M.

Potrero de los Funes, San Luis

Congreso; 47th Annual Meeting Argentine Society for Biochemistry and Molecular Biology (XLVII Reunión annual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2011

SOCIEDAD ARGENTINA DE INVESTIGACIN EN BIOQUIMICA Y BIOLOGIA MOLECULAR

Background: Doxorubicin (D) is an anticancer agent that hasimportant toxic effects and low water solubility. Gangliosidesspontaneously self-assemble in water as micelles and have beenshown to increase water solubility of Paclitaxel (Ptx).Objective: Characterization of the interactions between Ptx, D andganglioside micelles (water-solubility, structure, stability,cytotoxicity).Methods: UV-Vis spectrometry, DLS, EM and chromatographywere used to characterize water-solubility and structure. Hep-2 andHeLa cell cultures were used to assess cytotoxicity.Results: GM1 micelles increase water solubility of D up to 20mg/mL leading to a micellar structure that protects D from alkalinehydrolysis. Similar results are obtained with Ptx:GM1 (1:20 molarratio) micelles. However, incorporation of D into GM1 micellesimpairs the incorporation of Ptx. Ternary micelles have greaterstability than any of the components. Micelles are reorganized upondrug loading leading to smaller structures with a mean diameter of10 nm. In vitro assays show that both drugs penetrate into HeLa andHep-2 cells and are directed to microtubules (Ptx) and the cellnucleus (D).Conclusions: GM1 spontaneously loads Ptx and D into differentnano-domains of stable and water soluble 10 nm micelles thatdeliver the drugs to HeLa and Hep-2 cells similarly than therespective free drugs. Co-delivery of Ptx and D enhancechemotherapy in vitro.