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Title

Anti-Inflammatory Polymeric Nanoparticles Based on Ketoprofen and Dexamethasone

AuthorsEspinosa-Cano, Eva; Aguilar, María Rosa ; Portilla, Yadileiny; Barber, Domingo F. ; San Román, Julio
KeywordsNanoparticles
Ketoprofen
Dexamethasone
Inflammation
Macrophages
M1 and M2 markers
Il12-p40 subunit
Issue Date2020
PublisherMultidisciplinary Digital Publishing Institute
CitationPharmaceutics 12(8): 723 (2020)
AbstractPolymeric nanoparticles that combine dexamethasone and naproxen reduce inflammation and synergistically inhibit Interleukin-12b (Il12b) transcription in macrophages. This effect can be the result of a cyclooxygenase-dependent or a cyclooxygenase-independent mechanism. The aim of this work is to obtain potent anti-inflammatory polymeric nanoparticles by the combination of dexamethasone and ketoprofen, one of the most efficient cyclooxygenase-inhibitors among non-steroidal anti-inflammatory drugs, with appropriate hydrodynamic properties to facilitate accumulation and co-release of drugs in inflamed tissue. Nanoparticles are spherical with hydrodynamic diameter (117 ± 1 nm), polydispersity (0.139 ± 0.004), and surface charge (+30 ± 1 mV), which confer them with high stability and facilitate both macrophage uptake and internalization pathways to favor their retention at the inflamed areas and lysosomal degradation and drug release, respectively. In vitro biological studies concluded that the dexamethasone-loaded ketoprofen-bearing system is non-cytotoxic and efficiently reduces lipopolysaccharide-induced nitric oxide release. The RT-qPCR analysis shows that the ketoprofen nanoparticles were able to reduce to almost basal levels the expression of tested pro-inflammatory markers and increase the gene expression of anti-inflammatory cytokines under inflammatory conditions. However, the synergistic inhibition of Il12b observed in nanoparticles that combine dexamethasone and naproxen was not observed in nanoparticles that combine dexamethasone and ketoprofen, suggesting that the synergistic trans-repression of Il12b observed in the first case was not mediated by cyclooxygenase-dependent pathways.
Description© 2020 by the authors.
Publisher version (URL)https://doi.org/10.3390/pharmaceutics12080723
URIhttp://hdl.handle.net/10261/218458
DOIhttp://dx.doi.org/10.3390/pharmaceutics12080723
E-ISSN1999-4923
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