Co-delivery of doxorubicin and piperine using niosomes exhibited enhanced cytotoxic and inhibitory effect on cancer stem cell markers in breast cancer cells.

Combination therapy with chemotherapy and phytochemical drugs is a promising cancer treatment method. In this study, noisome with Tween 20, span 40 and cholesterol in 80:20 ration was prepared for co-delivery of piperine (PIP) and doxorubicin (DOX) (Nio-DOX/PIP) using thin-layer hydration method. Niosomes indicated spherical structure, average size 653 ± 3.25 nm and a zeta potential of ∼-15.88 mV with an encapsulation efficiency of 84.15% and 67.50% for DOX and PIP, respectively. Release of DOX (69.25%) and PIP (35.10%) after 24 h from niosomal dispersion is less than free solution that indicate release of drug in a sustained way from niosomes. Combination index and isobologram analysis using CompuSyn software indicated that combination of DOX and PIP at IC concentration generated synergism anticancer effect (CI value <0.9). Nio-DOX/PIP (IC: 0.14/14 µM) exhibited greater inhibitory effect on viability of MCF-7 cells in comparison with free drugs (IC: 0.67/67 µM). Expression analysis using Real time PCR showed that Nio-DOX/PIP reduces expression of CD133 and ABCB (33-fold), CD44 (10-fold), ALDH1: (5.8-fold) and NANOG and SOX2 (more than 90%) significantly more than free DOX. In conclusion, results showed that PIP can potentiate cytotoxicity of DOX and niosomes are suitable carriers for encapsulation of PIP and DOX.