Vitamin D-Loaded Nanostructured Lipid Carrier (NLC): A New Strategy for Enhancing Efficacy of Doxorubicin in Breast Cancer Treatment

ABSTRACT

The dangerous dose-dependent side effects of anticancer agents triggered the finding of new approaches for elevated chemotherapy efficacy. This study investigated the potential application of nanostructured lipid careers (NLCs) in increasing vitamin D₃ (VitD) effectiveness in breast cancer cell (MCF-7) in concurrent administration with doxorubicin (Dox). VitD-loaded NLCs were characterized by particle size, zeta potential, Fourier transform infrared spectroscopy, and scanning electron microscope. Cytotoxicity and molecular effects of formulation were evaluated by MTT, DAPI staining, flow cytometry, and real-time quantitative PCR assays. The formulation revealed mean particle size of 87±5 nm with a polydispersity index of 0.24 confirmed by SEM images. The IC₅₀ values for VitD and Dox were 1.3 ± 0.04 and 0.65 ± 0.05 µM, respectively. VitD-loaded NLCs decreased the percentage of cell proliferation from 49 ± 7.2% to 37 ± 5.1% (P < 0.05). Cotreatment of the cells with VitD-loaded NLCs and Dox caused over a twofold increase in the percentage of apoptosis (P < 0.05). Gene expression profile demonstrated a significant decrease in antiapoptotic factor survivin along with increase in proapoptotic factor Bax mRNA levels. Overall, our results introduced the NLC technology as a novel strategy to elevate the efficacy of chemotherapeutics in breast cancer.

Funding

This work was financially supported by grant from Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. The authors are sincerely grateful to Drug Applied Research Center for providing the infrastructure requirement for successful accomplishment of this research.