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.

Cationic Niosomes as Non-Viral Vehicles for Nucleic Acids: Challenges and Opportunities in Gene Delivery

“…A triple combination of drugs in niosomes has also been described by Hemati et al [114]. In this study, DOX was encapsulated with the chemosensitizer quercetin.…”

“…Cytotoxicity assays in three cancer cell lines showed a higher toxicity of the niosome formulated drugs when compared to non-encapsulated drugs. In a non-cancer cell line the niosomal formulations were less toxic than the free drugs [114].…”

Development of a novel liposomal nanoparticle formulation of cisplatin to breast cancer therapy

“…An increase in the concentration of cholesterol leads to the augmentation of this component in the membrane bilayer, pulling out the drug from the liposomal bilayers and decreasing the critical packing parameter (CPP) can result in decreased entrapment efficiency . The presence of PEGylation in liposomal formulations enhanced the stability, diminishing the mean size diameter, increased entrapment efficiency and half‐life of the particles in blood circulation . According to the findings of the study, the addition of 5% PEG to the F1 formula caused smaller diameter, smaller PDI, and higher drug encapsulation.…”

The combined administration of parthenolide and ginsenoside CK in long circulation liposomes with targeted tLyp-1 ligand induce mitochondria-mediated lung cancer apoptosis

“…Combinations of traditional Chinese medicines have been widely used to treat various diseases, including cancer [33][34][35][36]. The main advantages of this approach are the ability to reduce the dose and toxicity of the individual compounds, and to minimize or delay the induction of drug resistance [30].…”