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

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 (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. RESULTS DxCb-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. CONCLUSION Our results indicate that the co-administration of dexamethasone and butyrate by nanoparticles may be beneficial for inflammatory bowel disease treatment.