Journal
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 157, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejps.2020.105601
Keywords
Nanomedicine; in vivo assays; macrophages; nociception
Categories
Funding
- S ~ao Paulo Research Foundation (FAPESP
- Brazil) [2017/10241-6, 2017/22919-7, 2018/00840-2]
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The study found that incorporating indomethacin into mesoporous silica nanoparticles can effectively alleviate pain and inflammation, while reducing the gastric and hepatic damage caused by indomethacin.
Purpose: We evaluated the analgesic, anti-inflammatory and toxicological effects of indomethacin incorporated into mesoporous silica nanoparticles (IND+NP). Methods: Nociception was evaluated by the formalin assay. The anti-inflammatory potential was assessed by cell migration and paw edema assays, modulation of nitric oxide and cytokines (IL-6, IL-10 and TNF-alpha) by macrophages production. Toxicity was evaluated in peritoneal macrophages and by the locomotion assay and assessment of gastric injuries, presence of occult blood and hepatic and renal markers. Results: IND+NP reduced nociception during phases 1 by 53% and 2 by 79% of the formalin assay and the influx of peritoneal cells by 94%, indicating an analgesic and anti-inflammatory effect more efficiently than indomethacin alone. Indomethacin, but not IND+NP, caused macroscopic gastric injuries, the presence of fecal occult blood, and an increase of ALT levels. In the paw edema assay, IND+NP reduced edema by 21%. IND+NP has no effect on the LPS-induced production of nitric oxide, IL-6, IL-10 and TNF-alpha on no cytotoxic concentrations. Conclusions: The incorporation of indomethacin into mesoporous silica nanoparticles effectively increased the activity of the drug observed in the formalin and cell migration assays and prevented the gastric and hepatic damage associated with its use.
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