Pharmaceutical Research

, Volume 28, Issue 6, pp 1317–1327

String-Like Micellar Nanoparticles Formed by Complexation of PEG-b-PPA and Plasmid DNA and Their Transfection Efficiency

Authors

  • Xuan Jiang
    • Department of Materials Science and Engineering, and Whitaker Biomedical Engineering InstituteJohns Hopkins University
  • Derek Leong
    • Department of Materials Science and Engineering, and Whitaker Biomedical Engineering InstituteJohns Hopkins University
  • Yong Ren
    • Department of Materials Science and Engineering, and Whitaker Biomedical Engineering InstituteJohns Hopkins University
  • Zhiping Li
    • Department of MedicineJohns Hopkins University School of Medicine
  • Michael S. Torbenson
    • Department of PathologyJohns Hopkins University School of Medicine
    • Department of Materials Science and Engineering, and Whitaker Biomedical Engineering InstituteJohns Hopkins University
Research Paper

DOI: 10.1007/s11095-011-0436-3

Cite this article as:
Jiang, X., Leong, D., Ren, Y. et al. Pharm Res (2011) 28: 1317. doi:10.1007/s11095-011-0436-3

ABSTRACT

Purpose

To investigate the gene delivery efficiency of string-like PEG-b-PPA/DNA micellar nanoparticles in the liver after intravenous injection and intrabiliary infusion.

Methods

PEG-b-PPA/DNA micellar nanoparticles were prepared in aqueous solution through spontaneous self-assembly between plasmid DNA and PEG10K-b-PPA4K or PEG10K-b-PP13K polymer. The stability of these micellar nanoparticles in different physiological media was evaluated by monitoring the particle size change of micellar nanoparticles with dynamic light scattering (DLS). The transfection efficiency of string-like PEG-b-PPA/DNA micellar nanoparticles in the liver was examined and compared with that of PPA/DNA nanoparticles after intravenous and intrabiliary infusion.

Results

These PEG-b-PPA/DNA micellar nanoparticles exhibited unique string-like morphology under TEM. The stability of these string-like nanoparticles in salt-, serum- or bile- containing media was significantly improved compared with PPA/DNA nanoparticles. More importantly, these PEG-b-PPA/DNA nanoparticles mediated 10-fold higher transfection efficiency than PPA/DNA nanoparticles in rat liver when delivered via intrabiliary infusion. In addition, histopathological data revealed that the PEG-b-PPA/DNA nanoparticles induced minimal level of liver toxicity or damage.

Conclusions

These string-like PEG-b-PPA/DNA micelles can mediate efficient transgene expression in the liver after bile duct infusion, and they have great potential to be used as effective gene carriers for liver-targeted gene delivery.

KEY WORDS

block copolymerDNA micellar nanoparticlesliver-targeted gene deliverymorphologystring-like

ABBREVIATIONS

PEG

polyethylene glycol

PPA

polyphosphoramidate

RII

retrograde intrabiliary infusion

TIBA

triisobutylaluminum

Copyright information

© Springer Science+Business Media, LLC 2011