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Solid lipid nanoparticles delivering anti-inflammatory drugs to treat inflammatory bowel disease: Effects in an in vivo model 被引量:3

Solid lipid nanoparticles delivering anti-inflammatory drugs to treat inflammatory bowel disease: Effects in an in vivo model
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摘要 To improve anti-inflammatory activity while reducing drug doses, we developed a nanoformulation carrying dexamethasone and butyrate.METHODSDexamethasone cholesteryl butyrate-solid lipid nanoparticles (DxCb-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 lipopolysaccharide-induced 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 concentrations.RESULTSDxCb-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 DxCb 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, DxCb-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; DxCb-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%, respectively.CONCLUSIONOur results indicate that the co-administration of dexamethasone and butyrate by nanoparticles may be beneficial for inflammatory bowel disease treatment. AIM To improve anti-inflammatory activity while reducing drug doses, we developed a nanoformulation carrying dexamethasone and butyrate.METHODS 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 concentrations.RESULTS 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%, respectively.CONCLUSION Our results indicate that the co-administration of dexamethasone and butyrate by nanoparticles may be beneficial for inflammatory bowel disease treatment.
出处 《World Journal of Gastroenterology》 SCIE CAS 2017年第23期4200-4210,共11页 世界胃肠病学杂志(英文版)
基金 Supported by Regione Piemonte(grant“Converging Technologies”,Nano IGT) University of Torino(grant“Ricerca Locale”,Linea A)
关键词 NANOPARTICLES DEXAMETHASONE BUTYRATE Inflammatory bowel disease Drug delivery systems Nanoparticles;Dexamethasone;丁酸盐;煽动性的肠疾病;药交货系统
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