PMID- 15702489
OWN - NLM
STAT- MEDLINE
DCOM- 20050825
LR  - 20181201
IS  - 1099-498X (Print)
IS  - 1099-498X (Linking)
VI  - 7
IP  - 6
DP  - 2005 Jun
TI  - Enhanced intracellular uptake and inhibition of NF-kappaB activation by decoy 
      oligonucleotide released from PLGA microspheres.
PG  - 771-81
AB  - BACKGROUND: Nuclear factor-kappaB (NF-kappaB) transcription factor regulates the 
      expression of genes involved in immune response and inflammation. NF-kappaB 
      activity can be efficiently inhibited by double-stranded oligodeoxynucleotides 
      (ODNs). In the present study, we investigated the potential of 
      poly(DL-lactic-co-glycolic acid) (PLGA) microspheres as delivery system for an 
      ODN against NF-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide 
      (LPS). METHODS: Microspheres encapsulating ODN were prepared by the multiple 
      emulsion/solvent evaporation technique and characterised in terms of size, 
      morphology, encapsulation efficiency and in vitro release profile. In vitro 
      uptake after 4 h and activity of ODN released from microspheres were evaluated in 
      RAW 264.7 macrophages stimulated with LPS for 24, 48 and 72 h. RESULTS: We 
      prepared microspheres with a high encapsulation efficiency showing a very slow 
      and almost constant in vitro release of ODN for up to 1 month. ODN slowly 
      released from microspheres translocated better into LPS-stimulated cells as 
      compared with naked ODN. Incubation of cells with ODN-encapsulating microspheres 
      resulted in a decrease of tumor necrosis factor-alpha (TNF-alpha) and nitrite 
      production, inducible nitric oxide synthase (iNOS) protein expression, as well as 
      NF-kappaB/DNA-binding activity. Similar results were obtained with naked ODN only 
      at about 80 times higher concentrations. CONCLUSIONS: Our results suggest that 
      PLGA microspheres could be a useful tool to improve pharmacokinetics of a ODN 
      decoy to NF-kappaB and may represent a promising strategy to effectively inhibit 
      the transcriptional activity of NF-kappaB in inflammatory process.
CI  - Copyright (c) 2005 John Wiley & Sons, Ltd.
FAU - De Rosa, Giuseppe
AU  - De Rosa G
AD  - Dipartimento di Chimica Farmaceutica e Tossicologica, Universita degli Studi di 
      Napoli Federico II, Via Montesano 49, 80131 Naples, Italy.
FAU - Maiuri, Maria Chiara
AU  - Maiuri MC
FAU - Ungaro, Francesca
AU  - Ungaro F
FAU - De Stefano, Daniela
AU  - De Stefano D
FAU - Quaglia, Fabiana
AU  - Quaglia F
FAU - La Rotonda, Maria Immacolata
AU  - La Rotonda MI
FAU - Carnuccio, Rosa
AU  - Carnuccio R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Gene Med
JT  - The journal of gene medicine
JID - 9815764
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitrites)
RN  - 0 (Oligonucleotides)
RN  - 0 (Polymers)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
RN  - 26009-03-0 (Polyglycolic Acid)
RN  - 33X04XA5AT (Lactic Acid)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Delayed-Action Preparations/chemistry
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme Activation/*drug effects
MH  - Enzyme Inhibitors/*pharmacology
MH  - Gene Expression
MH  - Gene Transfer Techniques
MH  - Lactic Acid/*chemistry
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages, Peritoneal/drug effects/enzymology/metabolism
MH  - Mice
MH  - Microscopy, Electron, Scanning
MH  - *Microspheres
MH  - Mutation
MH  - NF-kappa B/chemistry/genetics/*metabolism
MH  - Nitric Oxide Synthase/genetics/metabolism
MH  - Nitric Oxide Synthase Type II
MH  - Nitrites/analysis/metabolism
MH  - Oligonucleotides/*metabolism/pharmacokinetics/pharmacology
MH  - Polyglycolic Acid/*chemistry
MH  - Polylactic Acid-Polyglycolic Acid Copolymer
MH  - Polymers/*chemistry
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2005/02/11 09:00
MHDA- 2005/08/27 09:00
CRDT- 2005/02/11 09:00
PHST- 2005/02/11 09:00 [pubmed]
PHST- 2005/08/27 09:00 [medline]
PHST- 2005/02/11 09:00 [entrez]
AID - 10.1002/jgm.724 [doi]
PST - ppublish
SO  - J Gene Med. 2005 Jun;7(6):771-81. doi: 10.1002/jgm.724.