Preparation and protective effects of 1,8-cineole-loaded self-microemulsifying drug delivery system on lipopolysaccharide-induced endothelial injury in mice.

Abstract An optimised 1,8-cineole-loaded self-microemulsifying drug delivery system (CIN-SMEDDS) with a mean droplet size, polydispersity index, mean zeta potential and encapsulation efficiency of 38.14 ± 1.47 nm, 0.208 ± 0.036, −9.312 ± 1.764 mV and 95.35% ± 1.13%, respectively, successfully ameliorated the lipopolysaccharide (LPS)-induced endothelial injury in mice. Acute toxicity assay in mice through the oral administration of CIN-SMEDDS showed that the median lethal dose of CIN-SMEDDS was 2998.9 mg/kg. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated that the cytotoxicity of CIN-SMEDDS to Caco-2 cells may be ascribed to the surfactant/co-surfactant mixture. In particular, CIN-SMEDDS remarkably inhibited inflammatory cytokines IL-1β, IL-6 and IL-8 with a simultaneous increase in IL-10 in LPS-treated mice. Haematoxylin-eosin staining results showed that CIN-SMEDDS attenuated LPS-induced vascular endothelial injury. Western blot results showed that the vascular protective effects of CIN-SMEDDS were associated with the NF-κB and peroxisome proliferator-activated receptor γ signalling pathways. These findings indicated that CIN-SMEDDS can attenuate LPS-induced endothelial injury and thus was proposed as a promising agent for the treatment of inflammatory cardiovascular disease. [ABSTRACT FROM AUTHOR]