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The AAPS Journal

, 11:445 | Cite as

Influence of the Molecular Weight of Bioreducible Oligoethylenimine Conjugates on the Polyplex Transfection Properties

  • Haijun YuEmail author
  • Verena Russ
  • Ernst Wagner
Research Article

Abstract

The purpose of the present study was to investigate the influence of molecular weights on the chemical, biophysical, and biological properties of bioreducible oligoethylenimine conjugates. The cationic conjugates were synthesized by polyaddition between branched oligoethylenimine 800 Da (OEI) and the disulfide bond containing N,N′-cystamine bisacrylamide (CBA) linker. A correlation between the copolymer molecular weights and the polyplex transfection properties was found. The OEI–CBA copolymers differing in molecular weights (from 8.6 to 37 kDa) showed good plasmid DNA binding ability resulting in compact 90- to 150-nm-sized polyplexes. Colloidal stability of the polyplexes was lost in reductive environment. A low concentration of dithiothreitol of 5 µM was sufficient to render polyplexes unstable in size. Reducing conditions at physiological salt concentration triggered polyplex dissociation. The bioreducible polymers displayed much lower cytotoxicity (IC50 ∼ 100 μg/mL in cell culture) than branched polyethylenimine 25 kDa (BPEI) and linear polyethylenimine 22 kDa (LPEI). Reporter gene transfection experiments were done with CHO-K1 and B16-F10 cells. The largest (37 kDa) copolymer HC-6-8 demonstrated highest transfection levels among all the bioreducible copolymers, which was comparable with LPEI and much more effective than BPEI.

Key words

bioreducible gene delivery PEI polyplexes synthetic vectors 

Abbreviations

BPEI

Branched PEI 25 kDa

CBA

N,N′-cystamine bisacrylamide

DLS

Dynamic light scattering

DTT

Dithiothreitol

GPC

Gel permeation chromatograph

HC

High concentration

HMW

High molecular weight

LC

Low concentration

LMW

Low molecular weight

LPEI

Linear PEI 22 kDa

MWCO

Molecular weight cutoff

OEI

Oligoethylenimine 800 Da

pDNA

Plasmid DNA

Notes

Acknowledgment

We thank Ms Olga Brück for skilful assistance in preparing the manuscript, Ms. Terese Magnusson and Dr. Michael Günther for their assistance in FACS measurement. We acknowledge the financial support by DFG SPP1230, excellence cluster NIM and EC project GIANT.

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Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  1. 1.Pharmaceutical Biology–Biotechnology, Center of Drug Research, Department of Pharmacy, and Center for Nanoscience (CeNS)Ludwig-Maximilians UniversitätMunichGermany

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