Novel Soluplus®-TPGS mixed micelles for encapsulation of paclitaxel with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines

Authors
Bernabeu, Ezequiel Adrian; Gonzalez, Lorena; Cagel, Carlos Maximiliano; Gergic, Esteban P.; Moretton, Marcela Analía; Chiappetta, Diego Andrés
Publication Year
2016
Language
English
Format
article
Status
Published version
Description
The aim of this work was to develop mixed micelles based on two biocompatible copolymers of polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus®) and D-α-tocopheryl polyethylene-glycol 1000 succinate (TPGS), to improve the aqueous solubility and the in vitro anti-tumor activity of paclitaxel (PTX). Pure and mixed nanomicelles were prepared by solvent evaporation method and characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Solubility of PTX was increased 60,000 and 38,000 times, when it was formulated in pure Soluplus® micelles and in mixed micelles (Soluplus®:TPGS; 4:1 ratio), respectively. The in vitro PTX release profile from micellar systems was characterized employing the dialysis membrane method where all drug-loaded formulations showed a sustained and slow release of PTX. In vitro assays were conducted on human cancer cell lines including ovarian cancer cells SKOV-3, breast cancer cells MCF-7 and triple negative breast cancer cells MDA-MB-231. Cytotoxicity studies showed that mixed micelles exhibited better antitumor activity compared to PTX solution against the three cell lines. Furthermore mixed micelles showed a significant increase on PTX cellular uptake in comparison with pure Soluplus® micelles and free drug in all cell lines assayed. More important, blank mixed micelles have shown cytotoxic activity due to the ability of TPGS to induce apoptosis in cancer cells. This effect was associated with the expression levels of cleaved-PARP, an apoptosis-related protein. On the basis of these results, the mixed micelles developed in this study might be a potential nano-drug delivery system for cancer chemotherapy.
Fil: Bernabeu, Ezequiel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Gonzalez, Lorena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología; Argentina
Fil: Cagel, Carlos Maximiliano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Gergic, Esteban P.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Moretton, Marcela Analía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Fil: Chiappetta, Diego Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina
Subject
BREAST AND OVARIAN CANCER CELL LINES
IN VITRO ANTI-TUMORAL ACTIVITY
PACLITAXEL ENCAPSULATION
SOLUPLUS®-TPGS MIXED MICELLES
Otras Ciencias Médicas
Otras Ciencias Médicas
CIENCIAS MÉDICAS Y DE LA SALUD
Otras Ciencias Médicas
Otras Ciencias Médicas
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/17516