Polyamines in the Surface of Lipid Micelles Improve the Cellular Uptake of Antitumoral Agents

Purpose: The ability of spermidine to increase the selectivity of anticancer agents has been studied extensively. In this research we report the combination of this polyamine and GM1 ganglioside micelles and characterize their behavior for drug delivery. Methods: Dynamic light scattering and electron microscopy were used to characterize size and morphology of micelles. Zeta potential was determined using a Nano-zeta potential analyzer. Size-exclusion chromatography was used to separate different populations. Cytotoxic effect of micelles was evaluated on Hep2 cell line. Results: Covalent conjugation of spermidine to gangliosides produces a clear reduction of the electronegative z potential of micelle surface. DLS analysis shows no significant differences between both micelles, while TEM image shows a smaller size of Spermidine-GM1. These modified micelles load hydrophilic or hydrophobic antitumor drugs and conjugation does not affect the stability of micelles/drug in solution. Spermidine-GM1/Doxo micelles show faster drug release into cells as compared with GM1/Doxo micelles; however, no evidence can be found for the participation of the polyamine transport system in the uptake of modified micelles. Conclusion: While Spermidine-GM1 and GM1 micelles show similar physical properties, spermidine modified micelles are most efficient to release drugs, making this an interesting alternative to consider for drug delivery.