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

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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.

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Acknowledgments

The author would like to dedicate this article to Prof. Dr. John Samuel, who passed away far too soon. We thank him and Praveen Elamanchili from the Faculty of Pharmacy at the University of Alberta for their awesome support during the first experiments with CpG ODNs. We thank Nadja Sandholzer for expert technical assistance. This study was supported by grants BMBF Biofuture 0311896 to G.H, and from the Else-Kröner Fresenius Foundation and the German Research Foundation (DFG En 169/7-2 and GK 1202) to C.B. and S.E.

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Authors and Affiliations

  1. Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University, Butenandtstr. 5-13, 81377, Munich, Germany

    Klaus Zwiorek, Gerhard Winter & Conrad Coester

  2. Department of Internal Medicine, Division of Clinical Pharmacology, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336, Munich, Germany

    Carole Bourquin, Julia Battiany & Stefan Endres

  3. Department of Internal Medicine, Division of Clinical Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Gunther Hartmann

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  1. Klaus Zwiorek
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  2. Carole Bourquin
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  7. Conrad Coester
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Correspondence to Conrad Coester.

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Zwiorek, K., Bourquin, C., Battiany, J. et al. Delivery by Cationic Gelatin Nanoparticles Strongly Increases the Immunostimulatory Effects of CpG Oligonucleotides. Pharm Res 25, 551–562 (2008). https://doi.org/10.1007/s11095-007-9410-5

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  • DOI: https://doi.org/10.1007/s11095-007-9410-5

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