A glucose-targeted mixed micellar formulation outperforms Genexol in breast cancer cells.

EZEQUIEL BERNABEU; MARCELA BEATRIZ ZUBILLAGA; EZEQUIEL BERNABEU; MARCELA BEATRIZ ZUBILLAGA; MARCELA A. MORETTON; GONZALEZ LORENA; MARCELA A. MORETTON; GONZALEZ LORENA; GROTZ ESTEFANIA; DIEGO A. CHIAPPETTA; GROTZ ESTEFANIA; DIEGO A. CHIAPPETTA

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2017 vol. 114 p. 305 - 316

0939-6411

Breast cancer represents the top cancer among women, accounting 521.000 deaths per year. Development of targeted nanomedicines to breast cancer tissues represents a milestone to reduce chemotherapy side effects. Taking advantage of the over-expression of glucose (Glu) membrane transporters in breast cancer cells, we aim to expand the potential of a paclitaxel (PTX)-loaded mixed micellar formulation based on polyvinyl caprolactam-polyvinylacetate-polyethylene glycol graft copolymer (Soluplus®) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) by its surface decoration with Glu moieties. The glycopolymer (Soluplus(Glu)) was obtained by microwave-assisted ring opening reaction of δ-gluconolactone initiated by Soluplus®. The glycosylation was confirmed by 1H NMR and by agglutination assays employing Concanavalin A. The hydrodynamic diameter of Soluplus(Glu) micelles was characterized by dynamic light scattering (100.3 ± 3.8 nm) as well as the critical micellar concentration value (0.0151% w/v). Then, a mixed micelle formulation employing Soluplus®, Soluplus(Glu) and TPGS (3:1:1 wt ratio) loaded with PTX (4 mg/mL) was developed as a multifunctional nanocarrier. Its in vitro anticancer performance in MCF-7 (1.6-fold) and MDA-MB-231 (14.1-fold) was significantly enhanced (p < 0.05) versus the unique commercially available micellar-based PTX-nanoformulation (Genexol®). Furthermore, the in vitro PTX cellular uptake assays revealed that the drug intracellular/cell content was significantly (p < 0.05) higher for the Glu-containing mixed micelles versus Genexol® after 6 h of incubation with MCF-7 (30.5-fold) and MDA-MB-231 (5-fold). Overall, results confirmed the potential of our Glu-decorated mixed colloidal formulation as an intelligent nanocarrier for PTX-targeted breast cancer chemotherapy.