Pharmaceutical Research

, Volume 25, Issue 3, pp 551–562

Delivery by Cationic Gelatin Nanoparticles Strongly Increases the Immunostimulatory Effects of CpG Oligonucleotides

Authors

  • Klaus Zwiorek
    • Department of Pharmacy, Pharmaceutical Technology and BiopharmaceuticsLudwig-Maximilians-University
  • Carole Bourquin
    • Department of Internal Medicine, Division of Clinical PharmacologyLudwig-Maximilians-University
  • Julia Battiany
    • Department of Internal Medicine, Division of Clinical PharmacologyLudwig-Maximilians-University
  • Gerhard Winter
    • Department of Pharmacy, Pharmaceutical Technology and BiopharmaceuticsLudwig-Maximilians-University
  • Stefan Endres
    • Department of Internal Medicine, Division of Clinical PharmacologyLudwig-Maximilians-University
  • Gunther Hartmann
    • Department of Internal Medicine, Division of Clinical PharmacologyUniversity of Bonn
    • Department of Pharmacy, Pharmaceutical Technology and BiopharmaceuticsLudwig-Maximilians-University
Research Paper

DOI: 10.1007/s11095-007-9410-5

Cite this article as:
Zwiorek, K., Bourquin, C., Battiany, J. et al. Pharm Res (2008) 25: 551. doi:10.1007/s11095-007-9410-5

Abstract

Purpose

Cationized gelatin nanoparticles (GNPs) were used as carrier to improve delivery of immunostimulatory CpG oligonucleotides (CpG ODN) both in vitro and in vivo.

Methods

Uptake of CpG ODN-loaded cationized gelatin nanoparticles (CpG-GNPs) into murine myeloid dendritic cells (DCs) and their respective immunostimulatory activity was monitored. In vivo, induction of cytokine secretion by CpG-GNPs was measured. For experiments on primary human cells, prototypes of the three CpG ODN classes were adsorbed onto GNPs. Uptake and induction of proinflammatory cytokines were assessed in human plasmacytoid DCs and B cells, the only existing human target cells for CpG ODN.

Results

In the murine system, gelatin nanoparticle formulations enhanced the uptake and immunostimulatory activity of CpG ODN both in vitro and in vivo. Furthermore, delivery by cationized gelatin nanoparticles of CpG ODN of the classes B and C to primary human plasmacytoid DCs increased production of IFN-α, a key cytokine in the driving of both the innate and adaptive immune responses.

Conclusion

GNPs can be used as a biodegradable and well tolerated carrier to deliver CpG ODN to their target cells and strongly increase activation of the immune system. This concept may be applied as novel adjuvant for antiviral and antitumoral vaccines.

Key words

adjuvantB cellsCpG oligonucleotidedendritic cellsgelatin nanoparticles

Copyright information

© Springer Science+Business Media, LLC 2007