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

• Published in: World journal of gastroenterology : WJG Vol. 23; no. 23; pp. 4200 - 4210
• Main Authors: Dianzani, Chiara, Foglietta, Federica, Ferrara, Benedetta, Rosa, Arianna Carolina, Muntoni, Elisabetta, Gasco, Paolo, Della Pepa, Carlo, Canaparo, Roberto, Serpe, Loredana
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 21.06.2017
• Subjects: Animals; Anti-Inflammatory Agents - administration & dosage; Basic Study; Butyrates - administration & dosage; Cell Adhesion; Colitis - chemically induced; Colitis - metabolism; Cytokines - metabolism; Dexamethasone - administration & dosage; Drug Delivery Systems; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Inflammatory Bowel Diseases - drug therapy; Leukocytes, Mononuclear - cytology; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Nanoparticles - chemistry; Neutrophils - cytology; Inflammatory bowel disease; Nanoparticles; Drug delivery systems; Dexamethasone; Butyrate
• ISSN: 1007-9327; 2219-2840; 2219-2840
• DOI: 10.3748/wjg.v23.i23.4200

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.