Pharmaceutical Research

, Volume 25, Issue 3, pp 605–615 | Cite as

Targeted Delivery of Complexes of Biotin–PEG–Polyethylenimine and NF-κB Decoys to Brain-derived Endothelial Cells in Vitro

  • Raktima Bhattacharya
  • Berit Osburg
  • Dagmar Fischer
  • Ulrich Bickel
Research Paper



To evaluate the effect of re-directing the uptake mechanism of polyplexes containing oligodeoxynucleotide (ODN) decoys to nuclear factor kappa B (NF-κB) from absorptive-mediated to receptor-mediated endocytosis.

Materials and Methods

Complexes of ODNs and a co-polymer of biotin–polyethylenglycol and polyethylenimine (BPP) were targeted to brain-derived endothelial cells with a conjugate of antibody 8D3 and streptavidin (8D3SA). Size and stability of ODN/BPP complexes was measured by dynamic light scattering. Cellular uptake was studied by confocal microscopy. Cell viability and pharmacological effects were investigated on murine bEnd5 cells stimulated with tumor necrosis factor.


ODN/BPP complexes showed sizes of 116 ± 2.3 nm, which increased by 40 nm when coupled to 8D3SA, and were stable in physiological fluids. Targeted complexes were internalized intact into endosomal compartments. Treatment conditions, which yielded significant inhibitory effects on mRNA expression of VCAM-1, ICAM-1, IκBα and iNOS by bEnd5 cells, did not affect viability. At 0.5 μM, decoy ODN significantly inhibited monocyte adhesion to bEnd5 monolayers when delivered as 8D3SA-targeted complex, while higher concentrations of untargeted complex were ineffective.


The complex of NF-κB decoys and BPP, which can be targeted to transferrin receptors, is a promising drug candidate for neuroinflammatory diseases affecting the blood–brain barrier.

Key words

blood–brain barrier drug delivery polyethylenimine transferrin receptor transcription factor decoy 



blood–brain barrier


2′,7′-bis-(carboxyethyl)-5-(6)-carboxyfluorescein-acetoxymethyl ester




intercellular adhesion molecule 1


low molecular weight polyethylenimine


nuclear factor kappaB




poly (ethylene glycol)






sulfosuccinimidyl 4-[p-maleimidophenyl]butyrate


vascular cell adhesion molecule 1





The authors thank Dr. Holger Petersen (Basel) for synthesis and analysis of the biotin-PEG-PEI copolymer and Young Tag Ko for preparation of the rhodamine-biotin-PEG-PEI conjugate. We appreciate the helpful discussions with Dr. Thomas Kissel (Marburg). This work was supported by grant 1R01NS045043 to UB.


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Raktima Bhattacharya
    • 1
  • Berit Osburg
    • 1
  • Dagmar Fischer
    • 1
    • 2
  • Ulrich Bickel
    • 1
  1. 1.Department of Pharmaceutical SciencesTexas Tech University Health Sciences Center School of PharmacyAmarilloUSA
  2. 2.Department of Pharmaceutics and BiopharmacyPhilipps-University of MarburgMarburgGermany

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