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Polyethylene glycol (PEG)‑modifications (PEGylations) of cationic liposome/small interfering RNA complexes (siRNA lipoplexes) can enhance their systemic stability. The present study determined the effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene‑silencing effects and siRNA biodistribution after intravenous injection. Three types of dialkyl or trialkyl cationic lipids were used in the current study for the preparation of cationic liposomes. Additionally, various PEGylated siRNA lipoplexes that contained PEG‑1,2‑distearoyl‑sn‑-glycero‑-3‑phosphoethanolamine (DSPE), PEG‑1,2‑distearoyl‑rac‑glycero‑3‑-methylpolyoxyethylene (DSG), PEG‑cholesterol (PEG‑Chol) and PEG‑chondroitin sulfate conjugate (PEG‑CS) were prepared. The results revealed that PEGylation of siRNA lipoplexes with PEG‑DSPE strongly decreased gene‑silencing effects in cells. In contrast, those with PEG‑DSG, PEG‑Chol and PEG‑CS did not largely decrease gene-silencing effects. However, regardless of the PEG‑derivative type, PEGylation of siRNA lipoplexes decreased their agglutination with erythrocytes. Furthermore, intravenous injection of PEGylated siRNA lipoplexes markedly decreased the accumulation of siRNA in the lungs, regardless of the type of PEG‑derivative. However, non‑PEGylated siRNA lipoplexes accumulated mainly in the lungs regardless of the siRNA lipoplex cationic lipid type. The results indicated that PEGylation of siRNA lipoplexes with PEG‑DSG, PEG‑Chol and PEG‑CS may improve systemic stability without losing transfection activity by PEGylation.

Effects of PEG anchors in PEGylated siRNA lipoplexes on in�vitro gene‑silencing effects and siRNA biodistribution in mice