Cationic liposomes for co-delivery of paclitaxel and anti-Plk1 siRNA to achieve enhanced efficacy in breast cancer

Combined effects of anticancer drug and siRNA have shown superior advantages for cancer chemotherapy. Herein, we analyzed the feasibility whether anticancer paclitaxel (PTX) and siRNA (siPlk1) could be co-delivered by cationic liposomes (CLs) to the tumor cells. Size and zeta potential of developed PTX loaded CLs (PTX-CLs) and siPlk1 complexed CLs (siPlk1-CLs) were 99.15 +/- 7.9 nm, 13.2 +/- 1.5 mV and 227.90 +/- 1.21 nm, 11.96 +/- 1.55 mV, respectively. In vitro drug release of PTX-CLs showed sustained release of PTX fill 168 h. PTX-CLs increased the biological half-life of PTX from 6.10 +/- 1.44 h to 16.3 +/- 3.61 h compared to the marketed PTX formulation. MCF-7 and MDA-MB-231 cell lines were used to study the anticancer activity of developed formulations. Cell uptake studies using FITC loaded CLs and FITC-conjugated-siPlk1 complexed CLs showed improved cellular internalization over FITC solution. Cytotoxicity studies showed enhanced anticancer activity for developed formulations over solutions, which may be due to their high cellular uptake and endosomal escape properties. Cell cycle analysis showed increased accumulation of cells in subG(1) and G(2)/M phase for individual as well as combination formulations over solutions. Therefore, we believed that CLs has potential ability to codeliver PTX and siRNA for chemotherapy.