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Solid lipid nanoparticles delivering anti-inflammatory drugs to treat inflammatory bowel disease: Effects in an in vivo model

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World Journal of Gastroenterology 2017年第23期23卷 4200-4210页

作者： Chiara Dianzani Federica Foglietta Benedetta Ferrara Arianna Carolina Rosa elisabetta muntoni Paolo Gasco Carlo Della Pepa Roberto Canaparo Loredana Serpe Department of Drug Science and Technology University of Torino Nanovector s.r.l

AIM To improve anti-inflammatory activity while reducing drug doses, we developed a nanoformulation carrying dexamethasone and *** Dexamethasone cholesteryl butyrate-solid lipid nanoparticles(Dx Cb-SLN) were obtained with the warm microemulsion method. The anti-inflammatory activity of this novel nanoformulation has been investigated in vitro(cell adhesion to human vascular endothelial cells and pro-inflammatory cytokine release by lipopolysaccharideinduced polymorphonuclear cells) and in vivo(disease activity index and cytokine plasma concentrations in a dextran sulfate sodium-induced mouse colitis) models. Each drug was also administered separately to compare its effects with those induced by their co-administration in SLN at the same *** Dx Cb-SLN at the lowest concentration tested(Dx 2.5 nmol/L and Cb 0.1 μmol/L) were able to exert a more than additive effect compared to the sum of the individual effects of each drug, inducing a significant in vitro inhibition of cell adhesion and a significant decrease of pro-inflammatory cytokine(IL-1β and TNF-α) in both in vitro and in vivo models. Notably, only the Dx Cb nanoformulation administration was able to achieve a significant cytokine decrease compared to the cytokine plasma concentration of the untreated mice with dextran sulfate sodium-induced colitis. Specifically, Dx Cb-SLN induced a IL-1β plasma concentration of 61.77% ± 3.19%, whereas Dx or Cb used separately induced a concentration of 90.0% ± 2.8% and 91.40% ± 7.5%, respectively; Dx Cb-SLN induced a TNF-α plasma concentration of 30.8% ± 8.9%, whereas Dx or Cb used separately induced ones of 99.5% ± 4.9% and 71.1% ± 10.9%, *** Our results indicate that the co-administration of dexamethasone and butyrate by nanoparticles may be beneficial for inflammatory bowel disease treatment.

关键词： Nanoparticles Dexamethasone 丁酸盐煽动性的肠疾病药交货系统

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