Effect of acyl chain length on transfection efficiency and toxicity of polyethylenimine

Aravindan, L., Bicknell, K. A. ORCID: https://orcid.org/0000-0002-5888-1424, Brooks, G., Khutoryanskiy, V. V. ORCID: https://orcid.org/0000-0002-7221-2630 and Williams, A. C. ORCID: https://orcid.org/0000-0003-3654-7916 (2009) Effect of acyl chain length on transfection efficiency and toxicity of polyethylenimine. International Journal of Pharmaceutics, 378 (1-2). pp. 201-210. ISSN 0378-5173 doi: 10.1016/j.ijpharm.2009.05.052

Abstract/Summary

Polyethylenimine (PEI) is an efficient nonviral gene delivery vector because of its high buffering capacity and DNA condensation ability. In our study, the amino groups on the polymeric backbone were acylated using acetic or propionic anhydride to alter the protonation behaviour and the hydrophilic/hydrophobic balance of the polymer. The concentration of acylated primary amines was determined using trinitrobenzene sulphonic acid assay. Results showed that our modified polymers had lower buffering capacities in solutions compared to PEI. The polymers were complexed with plasmid encoding enhanced green fluorescent protein at three different ratios (1:1, 1:2 and 1:10 w/w DNA to polymer) to form polyplexes and their toxicities and transfection efficiencies were evaluated in HEK 293 cells. Acylation reduced the number of primary amines on the polymer and the surface charge, improving haemocompatibility and reducing cytotoxicity. The reduction in the concentration of amino groups helped to optimise DNA compaction and facilitated polyplex dissociation in the cell, which increased transfection efficiency of the modified polymers compared to the parent polymer. Polymers with buffering capacities greater than 50% and less than 80% relative to PEI, showed higher transfection efficiencies than PEI. The propionic anhydride modified polymers had appropriate interactions with DNA which provided both DNA compaction and polyplex dissociation. These systems interacted better with the cell membrane because of their slightly higher lipophilicity and formed polyplexes which were less cytotoxic than polyplexes of acetic anhydride modified polymers. Among the vectors tested, 1:0.3 mol/mol PEI:propionic anhydride in a 1:2 w/w DNA:polymer composition provided the best transfection system with improved transfection efficiency and reduced cytotoxicity.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/4391
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > Thermal Analysis (CAF) Life Sciences > School of Biological Sciences Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Uncontrolled Keywords	Polyethylenimine; Buffering capacity; Nonviral vectors; Haemolysis; Transfection; Biocompatibility
Publisher	Elsevier
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