title: Sialoganglioside Micelles for Enhanced Paclitaxel Solubility: In Vitro Characterization.
abstract: Efficiency of mono-sialogangliosides to load Paclitaxel (Ptx) has recently been found to depend on the structure of the polysaccharide chain. In this study, we demonstrated that incorporation of only one more sialic acid into the ganglioside molecule, independently of its position, causes a 4-fold increase in Ptx-loading capacity, the maximum being at a 5:1 molar ratio (di-sialoganglioside/Paclitaxel, GD/Ptx). These complexes are stable in solution for at least 3 months, and over 90% of Ptx remains loaded in the micelles after extreme stress conditions such as high-speed centrifugation, lyophilization, or freeze-thaw cycles. Ganglioside micelles protect 50% of the initially loaded Ptx from alkaline hydrolysis after 24 h at pH 10. Dynamic light scattering studies revealed that GD micelles increase their size from 9 to 12 nm when loaded with Ptx. Transmission electron microscopy shows a homogeneous population of spherical micelles either with or without Ptx. In vitro biological activity was similar to that of the free drug. These results provide further options of self-assembled nanostructures of di- and tri-sialogangliosides with a higher loading capacity.
authors: Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR), Córdoba, Argentina.
authors: Valeria
authors: V
authors: Heredia
authors: Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR), Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Electronic address: v.alasino@gmail.com.
authors: Roxana V
authors: RV
authors: Alasino
authors: Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR), Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
authors: Victoria
authors: V
authors: Leonhard
authors: Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR), Córdoba, Argentina.
authors: Ariel G
authors: AG
authors: Garro
authors: Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; Departamento de Química Biológica-CIQUIBIC, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors: Bruno
authors: B
authors: Maggio
authors: Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR), Córdoba, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; Cátedra de Biotecnología, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba, Argentina. Electronic address: beltramodm@gmail.com.
authors: Dante M
authors: DM
authors: Beltramo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000737:chemistry*; D045744:Cell Line, Tumor; D002498:Centrifugation; D015195:Drug Design; D004355:Drug Stability; D005079:Excipients; D005612:Freeze Drying; D005615:Freezing; D005732:Gangliosides / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D008823:Micelles; D017239:Paclitaxel / Q000009:adverse effects / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005079:Excipients; D005732:Gangliosides; D008823:Micelles; C025447:sialogangliosides; D017239:Paclitaxel
keywords: cancer chemotherapy; drug delivery; drug design; micelles; nanoparticles