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

Abstract

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 IC₅₀ concentration generated synergism anticancer effect (CI value <0.9). Nio-DOX/PIP (IC₅₀: 0.14/14 µM) exhibited greater inhibitory effect on viability of MCF-7 cells in comparison with free drugs (IC₅₀: 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.