Self-assembled ganglioside micelles as nanodelivery vehicles of taxanes

V. LEONHARD; ALASINO R.V.; 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: Taxanes are anticancer agents that, due to their pooraqueous solubility, are formulated in vehicles associated with severeside effects. On the other side, gangliosides are amphipathicmolecules that spontaneously self-assemble in water as micelles.Objective: Characterization of the interactions between taxanes andganglioside micelles (water-solubility, structure, stability,cytotoxicity).Methods: UV-Vis spectrometry, DLS, EM and chromatographywere used to characterize water-solubility and structure. Humanlarynx hepithelioma cell cultures were used to assess cytotoxicity.Results: Water solubility of paclitaxel (Ptx) is 1 μg/mL and increasesup to 7 mg/mL upon its association with GM1 micelles. Theincorporation of Ptx in GM1 reaches an optimum at Ptx:GM1 1:20molar ratio. Loading of the Ptx into the micelle induces a structuralreorganization that leads to a reduction in size and an importantprotection of Ptx reducing its hydrolysis at alkaline pH. Diffusion ofeither GM1 or Ptx is restricted upon mixed-micelle formation. Invitro assays show that Ptx is incorporated by the cells and hasantimytotic 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. Complexesthus formed are more stable and do not affect the biologicalantimytotic activity of Ptx.