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Oligonucleotide decoy to NF-κB slowly released from PLGA microspheres reduces chronic inflammation in rat
- Source :
-
Pharmacological Research . Jul2009, Vol. 60 Issue 1, p33-40. 8p. - Publication Year :
- 2009
-
Abstract
- Abstract: Nuclear factor-κB (NF-κB) plays a key role in the expression of several genes involved in the immune and inflammatory process. Previously, we demonstrated that NF-κB activation can be significantly inhibited by a double stranded oligodeoxynucleotide (ODN). Nevertheless, the therapeutic use of ODN requires a delivery system able to improve poor crossing of cell membranes and rapid in vivo enzymatic degradation. Poly(d,l-lactide-co-glycolide) (PLGA) microspheres can increase ODN stability in biological environment and release the encapsulated drug in long time frames. Here, we used a decoy ODN against NF-κB and we investigated its effect, when administered in naked form or when delivered by PLGA micropsheres, in a rat model of chronic inflammation. The subcutaneous implant of λ-carrageenin-soaked sponges caused leukocyte infiltration and formation of granulation tissue which were inhibited up to 15 days by co-injection of microspheres releasing decoy ODN whereas naked decoy ODN showed this effect only up to 5 days. Molecular analysis performed on granulation tissue demonstrated an inhibition of NF-κB activation correlated to a decrease of tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression. Our results suggest that microspheres could be an useful tool to improve pharmacokinetics of decoy ODN and may represent a strategy to inhibit NF-κB activation in chronic inflammation. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 10436618
- Volume :
- 60
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Pharmacological Research
- Publication Type :
- Academic Journal
- Accession number :
- 39359547
- Full Text :
- https://doi.org/10.1016/j.phrs.2009.03.012