Delivery by cationic gelatin nanoparticles strongly increases the immunostimulatory effects of CpG oligonucleotides.
OBJECTIVE
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-alpha, a key cytokine in the driving of both the innate and adaptive immune responses.


CONCLUSIONS
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.
Zwiorek
Klaus
K
Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-University, Butenandtstr. 5-13, 81377, Munich, Germany.
Bourquin
Carole
C
Battiany
Julia
J
Winter
Gerhard
G
Endres
Stefan
S
Hartmann
Gunther
G
Coester
Conrad
C
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002412:Cations; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016898:Interferon-alpha / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D053758:Nanoparticles; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051217:Toll-Like Receptor 9 / Q000187:drug effects
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D002412:Cations; D016207:Cytokines; D004337:Drug Carriers; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D005780:Gelatin