Intravenous Nanocarrier for Improved Efficacy of Quercetin and Curcumin against Breast Cancer Cells: Development and Comparison of Single and Dual Drug-Loaded Formulations Using Hemolysis, Cytotoxicity and Cellular Uptake Studies.

The present work highlights the suitability of an oil-based nanocarrier to deliver quercetin (Q) and curcumin (C) through the intravenous route for treatment of breast cancer. The nanoemulsion prepared by the modified emulsification-solvent evaporation method resulted in particle size (<30 nm), polydispersity index (<0.2), zeta potential (<10 mV), optimum viscosity, high encapsulation efficiency and drug loading for both drugs. The pH and osmolarity of the nanoemulsion were about 7.0 and 280 mOsm, respectively, demonstrated its suitability for intravenous administration. In-vitro release of drugs from all the formulations demonstrated initial fast release followed by sustained release for a period of 48 h. The fabricated single and dual drug−loaded nanoemulsion (QNE, CNE, QC-NE) exhibited moderate hemolysis at a concentration of 50 μg/mL. The % hemolysis caused by all the formulations was similar to their individual components (p ˃ 0.05) and demonstrated the biocompatibility of the nanoemulsion with human blood. In vitro cytotoxic potential of single and dual drug−loaded nanoemulsions were determined against breast cancer cells (MF-7). The IC50 value for QNE and CNE were found to be 40.2 ± 2.34 µM and 28.12 ± 2.07 µM, respectively. The IC50 value for QC-NE was 21.23 ± 2.16 µM and demonstrated the synergistic effect of both the drugs. The internalization of the drug inside MF-7 cells was detected by cellular uptake study. The cellular uptake of QNE and CNE was approximately 3.9-fold higher than free quercetin and curcumin (p < 0.0001). This strategically designed nanoemulsion appears to be a promising drug delivery system for the proficient primary preclinical development of quercetin and curcumin as therapeutic modalities for the treatment of breast cancer.