PMID- 17570323
OWN - NLM
STAT- MEDLINE
DCOM- 20071024
LR  - 20070615
IS  - 1567-5769 (Print)
IS  - 1567-5769 (Linking)
VI  - 7
IP  - 8
DP  - 2007 Aug
TI  - Effects of intravenous and subcutaneous administration on the pharmacokinetics, 
      biodistribution, cellular uptake and immunostimulatory activity of CpG ODN 
      encapsulated in liposomal nanoparticles.
PG  - 1064-75
AB  - We have previously demonstrated that the immune response to an unmethylated 
      cytidine-guanosine (CpG)-containing oligonucleotide (ODN) is greatly enhanced 
      when encapsulated in a lipid nanoparticle (LN-CpG ODN). In this study, the 
      pharmacokinetics, biodistribution and cellular uptake of LN-CpG ODN following 
      intravenous (i.v.) and subcutaneous (s.c.) administration was characterized and 
      correlated with immunostimulatory activity. It is shown that, despite dramatic 
      differences in tissue distribution profiles and considerable differences in 
      uptake by CD11c-positive, CD11b-positive, Mac-3-positive and CD45R/B220-positive 
      cells following i.v. and s.c. administration, the resultant immune response is 
      very similar with respect to levels of cellular activation (DX5, Mac-3, CD11b, 
      CD45/B220, CD4, CD8 and CD11c) and cytolytic activity of immune cells [natural 
      killer (NK) cells and monocytes/macrophages] in the spleen and blood 
      compartments. Some differences in response kinetics and antibody-dependent 
      cellular cytotoxicity (ADCC) activity were noted in the peripheral blood NK cell 
      population. Analyses of particle biodistribution and cell types involved in 
      uptake leads to the conclusion that the inherent ability of antigen-presenting 
      cells (APCs) to sequester LN-CpG ODN results in efficient uptake of the particle, 
      even when present at very low concentrations, leading to similar responses 
      following i.v. and s.c. administration. These results contrast with the behavior 
      of free CpG ODN, for which distinctly different immune responses are observed 
      following i.v. or s.c. administration.
FAU - Wilson, Kaley D
AU  - Wilson KD
AD  - Department of Biochemistry and Molecular Biology, University of British Columbia, 
      Vancouver, British Columbia, Canada.
FAU - Raney, Sameersingh G
AU  - Raney SG
FAU - Sekirov, Laura
AU  - Sekirov L
FAU - Chikh, Ghania
AU  - Chikh G
FAU - deJong, Susan D
AU  - deJong SD
FAU - Cullis, Pieter R
AU  - Cullis PR
FAU - Tam, Ying K
AU  - Tam YK
LA  - eng
PT  - Journal Article
DEP - 20070502
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (CPG-oligonucleotide)
RN  - 0 (INEX 6303)
RN  - 0 (INX 6295)
RN  - 0 (Liposomes)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 10028-17-8 (Tritium)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage/blood/*pharmacokinetics
MH  - Animals
MH  - Antibody-Dependent Cell Cytotoxicity/drug effects/immunology
MH  - Antigen-Presenting Cells/drug effects/immunology/metabolism
MH  - Cell Membrane/metabolism
MH  - DNA/administration & dosage/chemistry/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Drug Compounding/methods
MH  - Female
MH  - Injections, Intravenous
MH  - Injections, Subcutaneous
MH  - Liposomes
MH  - Liver/metabolism
MH  - Lymph Nodes/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred ICR
MH  - Nanoparticles/*chemistry
MH  - Oligodeoxyribonucleotides/administration & dosage/chemistry/*pharmacokinetics
MH  - Spleen/metabolism
MH  - Time Factors
MH  - Tissue Distribution
MH  - Tritium
EDAT- 2007/06/16 09:00
MHDA- 2007/10/25 09:00
CRDT- 2007/06/16 09:00
PHST- 2007/01/11 00:00 [received]
PHST- 2007/04/02 00:00 [revised]
PHST- 2007/04/04 00:00 [accepted]
PHST- 2007/06/16 09:00 [pubmed]
PHST- 2007/10/25 09:00 [medline]
PHST- 2007/06/16 09:00 [entrez]
AID - S1567-5769(07)00104-X [pii]
AID - 10.1016/j.intimp.2007.04.002 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2007 Aug;7(8):1064-75. doi: 10.1016/j.intimp.2007.04.002. 
      Epub 2007 May 2.