Treatment with GM1-Ptx micelles leads to a potent inhibition of metastasis in a murine model of mammary gland cancer

LEONHARD V; ALASINO RV; PASQUALINI ME; CREMONEZZI, DC; GARCÍA N; BELTRAMO DM

Buenos Aires

Jornada; XX Jornadas Anuales de la Sociedad Argentina de Biología (SAB) XVII Jornadas de la Sociedad Uruguaya de Biociencias (SUB) Segundas Jornadas Rioplatenses de Biología; 2018

Sociedad Argentina de Biología

TREATMENT WITH GM1-PTX MICELLES LEADS TO A POTENT INHIBITION OFMETASTASIS IN A MURINE MODEL OF MAMMARY GLAND CANCER Leonhard Vab, Alasino RVab,Pasqualini MEbc, Cremonezzi DCd, García NHbc,Beltramo DMabe. aCentro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR); bConsejoNacional de Investigaciones Científicas y Técnicas (CONICET); cInstituto de Investigaciones en Ciencias de la Salud- FCM(INICSA-CONICET); dCátedra de Patología - Hospital Nacional de Clínicas - UniversidadNacional de Córdoba - Argentina; eFacultad de Ciencias Químicas -Universidad Católica de Córdoba ? Argentina. E-mail: vickyleonhard@hotmail.com  The formulation of GM1-Ptx micelles was developed with the objective ofreducing the toxicity related to the use of Taxol, Cremophor-based paclitaxeland to achieve an easy preparation methodology with greater stability than thatof Abraxane, Albumin-based paclitaxel. Acute toxicity of the micellarformulation was evaluated after intravenous administration in mice. The maximumtolerated dose (MTD) obtained for the GM1-Ptx formulation was 55 mg/kg whilethe lethal dose 50 % (LD50) was 70 mg/kg, this value being higher than that ofthe commercial formulations Taxol and Abraxane, with LD50 of 30 and 45 mg/kg,respectively. Antitumor activity, mortality and incidence of metastasis werestudied in a murine model of mammary gland cancer. The micellar formulation wasadministered i.v. at different doses for 9 weeks of treatment in comparisonwith the empty GM1 micelles and saline. After treatment, a completehistological examination of mice and the quantification of various biochemicalmarkers were performed. The treatment of cancerous mice with doses of 30 mg/kgper week achieved greater tumor regression, longer survival and lower incidenceof metastasis. When this dose is reached with two weekly administrations, thebest results were observed with the least presence of pulmonarymicrometastases.