Development and characterization of a novel cationic PEGylated niosome-encapsulated forms of doxorubicin, quercetin and siRNA for the treatment of cancer by using combination therapy

Abstract

The aim of this study was to optimize the cationic PEGylated niosome-containing anti-cancer drugs and siRNA to enhance the therapeutic response. Therefore, various surfactant-based (tween-60) vesicles of doxorubicin (DOX; a chemotherapeutic drug) and quercetin (QC; a chemosensitizer) were prepared. To load siRNA on niosomes, 1, 2-dioleoyl-3-trimethylammonium-propane (DOTAP) was used as a cationic lipid. The optimum formulation containing tween-60:cholesterol:DPPC:DOTAP:DSPE-PEG2000 at 49.5:5.5:15:25:5 demonstrated that the vesicle size and zeta potential were 52.8 ± 2.7 nm and +27.4 ± 2.3 mV, respectively. Entrapment efficiency (EE%) for DOX and QC was 86.4 ± 2.1% and 94.9 ± 3.9%, respectively. Moreover, the drug release during 6 h was 32.1 ± 1.6% and 30.5 ± 1.3% for DOX and QC, respectively denoted on the controlled release. The gel retardation assay demonstrated that siRNA could be successfully loaded into a cationic niosome:siRNA in a weight ratio 40:1. Additionally, noisome-encapsulated drugs had a higher toxicity against cancer cells when compared with un-encapsulated forms and the synergistic effects of co-delivery of siRNA and DOX with QC on gastric, prostate, breast cancer cells as well as human foreskin fibroblast as a normal cell line was shown. The results showed that the co-delivery of drugs and siRNA using cationic PEGylated niosomes exhibited an increased anti-cancer activity against the tumor cell death. It seems that cationic PEGylated niosomes have opened up a new avenue to enrich the armamentarium of therapeutic agents to fight cancer.