Institution: | 1. Department of Pharmacy, Ludwig-Maximilians-University Munich, Pharmaceutical Technology and Biopharmaceutics, Butenandtstr. 5–13, 81377 Munich, Germany;2. Department of Pharmacy, Ludwig-Maximilians-University Munich, Pharmaceutical Technology and Biopharmaceutics, Butenandtstr. 5–13, 81377 Munich, Germany
Department of Ophthalmology, University Eye Hospital Tübingen, Center for Ophthalmology, Elfriede-Aulhorn-Strasse 7, 72076 Tübingen, Germany;3. Department of Pharmacy, Ludwig-Maximilians-University Munich, Pharmaceutical Technology and Biopharmaceutics, Butenandtstr. 5–13, 81377 Munich, Germany
Department for Chemistry, University of Bern, Biochemistry and Pharmacy, Freiestrasse 3, Bern, 3012 Switzerland |
Abstract: | 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, different formulations of low molecular weight PEI (LMW-PEI) based copolymers polyethylenimine-g-polycaprolactone (PEI–PCL) (800 Da–40 kDa) and PEI–PCL–PEI (5–5–5 kDa) blended with or without polyethylene glycol-b-polycaprolactone (PEG–PCL) (5 kDa-4 kDa) are investigated to prepare nanoparticles via nanoprecipitation using a solvent displacement method with sizes ≈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 show 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 ≈40% as a result of the higher molecular weight PEI blocks. These results suggest that the PEI–PCL–PEI/PEG–PCL nanoparticle system could be a promising vehicle for siRNA delivery at minimal synthetic effort. |