Viral vector mimicking and nucleus targeted nanoparticles based on Dexamethasone conjugated Polyethylenimine nano-liposomes: Preparation and evaluation of transfection efficiency

Non-viral vectors such as polymers and liposomes have been used for gene delivery systems to overcome intrinsic problems of viral vectors, but transfection efficiency of these vectors is lower than viral vectors. In the present study, we conjugated dexamethasone (Dexa) to branched polyethylenimine (b-PEI), in combinations with cationic liposomes as a nonviral system to improve transfection efficiency. Cationic liposomes containing DOTAP and cholesterol were prepared by thin-film hydration following extrusion method. Dexamethasone mesylate was synthesized and conjugated to polyethylenimine by a one-step reaction. A novel gene delivery system, Lipopolyplex was developed by premixing liposome and different Mw of bPEI-Dexa as carriers following by addition of plasmid at three different C/P ratios. The resultant complexes were characterized for their size, zeta potential and ability of DNA condensation. Luciferase reporter gene was used for determination of transfection efficiency in neuro2A cells. Also, the toxicity of gene carriers was investigated in this cell line. Mean particle size of prepared complexes was less than 200 nm and there was no significant difference in size by increasing molecular weight of PEIs. All complexes had positive surface charge. Complete condensation of DNA was occurred at C/P ratio of 1 for all complexes. lipopolyplexes were more efficient than polyplexes and lipoplexes alone and transfection efficiency was improved by adding dexamethasone. Complexes containing liposome, PEI 10 kDa and dexamethasone had the highest transfection activity. Furthermore, non-viral vectors described in this study showed low cytotoxicity. The results of this study confirm that PEI in combination with liposome as lipopolyplex have low toxicity and may enhance transfection efficiency. Moreover, conjugation of dexamethasone to PEI, in combination with cationic liposome might be useful for the gene delivery