Liposome-mediated delivery of siRNA in lung cancer: formulation design parameters

Abdullah Alshehri, Anna Grabowska & Snow Stolnik

Lung cancer is considered a worthwhile target disease, based on high rate of incidence and death worldwide. Due to drawbacks of chemotherapy employed in the lung cancer treatment, research has recently focused on exploiting siRNA approach. However, the main bottleneck in applying siRNA clinically is its effective delivery to the cytosol of target cell. This work investigates siRNA delivery system based on liposomes comprising cationic lipid, 3ß-[N-(N’,N’-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol), and neutral lipid, dioleoylphosphatidylethanolamine (DOPE). The work shows that high level of siRNA encapsulation by a classical ‘film hydration’ method can be achieved, as confirmed by gel electrophoresis, even at relatively low cationic lipid to siRNA charge ratios (3.125:1 – 6.25:1). Cytotoxicity of the DC-Chol:DOPE liposomes per se in A549 (human epithelial lung cancer) cell culture is found dependent on both applied concentration and the molar ratio of the lipid components, with increased toxicity at higher cationic lipid content. In A549 cell culture, siRNA-liposome formulations prepared at different lipid compositions and at selected lipid-siRNA ratios, showed a reasonable cellular uptake, as observed by flow cytometry and fluorescence microscopy, indicating that these systems could represent a candidate formulation for siRNA delivery to lung cancer.

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