Linear PEI nanoparticles: efficient pDNA/siRNA carriers in vitro and in vivo

Linear polyethylenimine (lPEI, 25 kDa) nanoparticles' (LPN) series was synthesized by varying percentage of cross-linking with 1,4-butanediol diglycidyl ether (BDE) and their size, surface charge, morphology, pDNA protection/release, cytotoxicity and transfection efficiency were evaluated. Synthesized nanoparticles (NPs) were spherical in shape (size: similar to 109 - 235 nm; zeta potential: +38 to +16 mV). These NPs showed increased buffering capacity with increasing percent cross-linking and also exhibited excellent transfection efficiency (i.e., similar to 1.3 - 14.7 folds in case of LPN-5) in comparison with lPEI and the commercial transfection agents used in this study. LPN-5 based GFP-specific siRNA delivery resulted in similar to 86% suppression of targeted gene expression. These particles were relatively nontoxic in vitro (in cell lines) and in vivo (in Drosophila). In vivo gene expression studies using LPN-5 in Balb/c mice through intravenous injection showed maximum expression of the reporter gene in the spleen. These results together demonstrate the potential of these particles as efficient transfection reagents. From the Clinical Editor: The authors demonstrate a novel method of synthesizing linear PEI nanoparticles to utilize these as transfection agents. (C) 2012 Elsevier Inc. All rights reserved.