Liquid formulation containing doxorubicin-loaded lipid-core nanocapsules: Cytotoxicity in human breast cancer cell line and in vitro uptake mechanism

Cancer is a major public health problem in the world, being breast cancer the most frequent cancer affecting women. Despite advances in detection and treatment, mortality rates remain high. Therefore, new approaches for breast cancer treatments are necessary. In this study, our objective was to develop a liquid formulation containing doxorubicin-loaded lipid-core nanocapsules (DOX-LNC), to evaluate the in vitro antiproliferative activity and to determine the nanocapsules uptake by MCF-7 cells. Lipid-core nanocapsules (LNC), blank formulation, and DOX-LNC, proposed treatment, were prepared by self-assembling using the solvent displacement method. Hydrodynamic mean diameters (z-average) were respectively 191 +/- 31 nm and 230 +/- 23 nm presenting narrow size distributions. Drug content was 0.102 +/- 0.029 mg mL(-1) with an encapsulation efficiency higher than 90%. Formulations were applied to semiconfluent MCF-7 cells. After 24 h, LNC showed no cytotoxicity, while DOX-LNC showed an IC50 of 4.49 micromolar. After 72 h of incubation, DOX-LNC showed an IC50 of 1.60 micromolar demonstrating a sustained effect. The nanocapsules were internalized by endocytosis mediated by caveolin and by fluid phase endocytosis, which are active transport mechanisms. In conclusion, the liquid formulation containing DOX-LNC showed to be a promising product for the breast cancer treatment opening new avenues for further in vivo studies. (C) 2017 Elsevier B.V. All rights reserved.