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

作者：Moretton Marcela A; Bernabeu Ezequiel; Grotz Estefania; Gonzalez Lorena; Zubillaga Marcela; Chiappetta Diego A

来源：European Journal of Pharmaceutics and Biopharmaceutics, 2017, 114: 305-316.

DOI：10.1016/j.ejpb.2017.02.005

• Paclitaxel
• Polymeric mixed micelles
• Active targeting
• Glycosylated nanocarriers
• Breast cancer chemotherapy

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-a-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 delta-gluconolactone initiated by Soluplus. The glycosylation was confirmed by H-1 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((R))). 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((R)) 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.

• 出版日期2017-5