LAUSR

Polyethylenimine (PEI) is a commonly used cationic polymer for small-interfering RNA (siRNA) delivery due to its high transfection efficiency at low commercial cost. However, high molecular weight PEI is cytotoxic and thus, its practical application is limited. In this study, we investigated different formulations of low molecular weight PEI (LMW-PEI) based copolymers PEI-PCL (800 Da-40 kDa) and PEI-PCL-PEI (5 kDa-5 kDa-5 kDa) blended with or without PEG-PCL (5 kDa-4 kDa) to prepare nanoparticles via nanoprecipitation using a solvent displacement method with sizes around 100 nm. PEG-PCL can stabilize the nanoparticles, improve their biocompatibility, and extend their circulation time in vivo. The nanoparticles composed of PEI-PCL-PEI and PEG-PCL showed higher siRNA encapsulation efficiency than PEI-PCL/PEG-PCL based nanoparticles at low N/P ratios, higher cellular uptake, and a gene silencing efficiency of around 40% as a result of the higher molecular weight PEI blocks. These results suggested that the PEI-PCL-PEI/PEG-PCL nanoparticle system could be a promising vehicle for siRNA delivery at minimal synthetic effort. This article is protected by copyright. All rights reserved.