Solid lipid nanoparticles delivering anti- inflammatory drugs to treat inflammatory bowel disease: Effects in an in vivo model
Solid lipid nanoparticles delivering anti- inflammatory drugs to treat inflammatory bowel disease: Effects in an in vivo model
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DOI：
10.3748/wjg.v23.i23.4200
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发表时间：
2017-06-21
影响因子：
4.3
通讯作者：
Serpe, Loredana
中科院分区：
文献类型：
--
作者：
Dianzani, Chiara;Foglietta, Federica;Serpe, Loredana
目的制备地塞米松胆固醇丁酸酯固体脂质纳米粒（DxCb SLN），并对其抗炎活性进行评价。已经在体外（细胞粘附于人血管内皮细胞和脂多糖诱导的多形核细胞释放促炎细胞因子）和体内（葡聚糖硫酸钠诱导的小鼠结肠炎中的疾病活动指数和细胞因子血浆浓度）模型中研究了这种新型纳米制剂的抗炎活性。每种药物也分别给药，以比较其效果与在SLN中以相同浓度共同给药所诱导的效果。（Dx 2.5 nmol/L和Cb 0.1 μ mol/L）与每种药物的单独作用之和相比，能够发挥大于累加的作用，在体外和体内模型中诱导细胞粘附的显著体外抑制和促炎细胞因子（IL-1 β和TNF-α）的显著降低。值得注意的是，与患有葡聚糖硫酸钠诱导的结肠炎的未治疗小鼠的细胞因子血浆浓度相比，仅DxCb纳米制剂施用能够实现显著的细胞因子降低。具体而言，DxCb-SLN诱导的IL-1 β血浆浓度为61.77% +/-3.19%，而单独使用的Dx或Cb分别诱导的浓度为90.0% +/- 2.8%和91.40% +/-7.5%; DxCb-SLN诱导的TNF-α血浆浓度为30.8% ± 8.9%，而单独使用的Dx或Cb诱导的TNF-α血浆浓度为99.5% ± 4.9%和71.1% ± 10.9%，结论：地塞米松和丁酸钠纳米粒联合应用对炎症性肠病的治疗可能是有益的。
AIMTo 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 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.RESULTSDxCb-SLN at the lowest concentration tested (Dx 2.5 nmol/L and Cb 0.1 mu mol/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-1 beta and TNF-alpha) 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-1 beta 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-a 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.