Nerolidol-beta-cyclodextrin inclusion complex enhances anti-inflammatory activity in arthritis model and improves gastric protection.

Rheumatoid arthritis is an autoimmune inflammatory disease with progressive degradation of cartilage and joints. Additionally, gastric ulcer affects many patients who make prolonged use of non-steroidal anti-inflammatory drugs widely used in the symptomatic treatment of rheumatoid arthritis. Nerolidol, a natural sesquiterpene, has several biological activities including anti-inflammatory and antiulcerogenic action. This study aims to develop and characterize a nerolidol ß-cyclodextrin inclusion complex and to evaluate its activity in an experimental arthritis model. Inclusion complex was prepared by the lyophilization method and characterized by NMR, term analysis, XRD and SEM. Neutrophil migration assays and histopathological analysis were performed on zymosan-induced arthritis model using Swiss mice. And the gastroprotective effect was evaluated in two models of gastric ulcers: induced by ethanol and indomethacin. Inclusion complex showed no cytotoxicity and free nerolidol at a dose of 100 mg/kg (p.o.) in the arthritis model reduced neutrophil migration in 56% in relation to vehicle, and this inhibition was more expressive in the inclusion complex (67%) at the same dose. Histopathological analysis of the joint tissue confirmed the reduction of inflammatory signs. In the ethanol-induced gastric ulcer model, free nerolidol reduced the relative ulcer area more expressively (4.64%) than the inclusion complex (21.3%). However, in the indomethacin induction model, the inclusion complex showed better results in gastric protection compared to free nerolidol. The action of nerolidol complexed in beta-cyclodextrin in reducing arthritis inflammation combined with its gastroprotective action make it a potential new drug.

Anti-inflammatory effect of nano-encapsulated nerolidol on zymosan-induced arthritis in mice.

Nerolidol is naturally occurring sesquiterpene has wide range of biological properties including anti-inflammatory activity. However, it has high volatility with low solubility in nature. The present study aimed to develop and characterized nano-encapsulated nerolidol and evaluated its activity on zymosan-induced arthritis model. Nano-capsules were produced by interfacial deposition of preformed polymer method and characterized by particle size, pH, polydispersity index (PDI), zeta potential, drug content and transmission electron microscopy (TEM). In vitro cytotoxicity of formulations was evaluated by alamar blue and MTT assays. In vivo neutrophils migration assay was performed on intra-articular zymosan-induced arthritis model in mice. Nano-encapsulated nerolidol suspensions presented adequate properties: mean diameter of particles 219.5 ±â€¯8.4 nm, pH: 6.84 ±â€¯0.5, PDI≤0.2, the zeta potential was -20.3 ±â€¯3.6 mV and drug content 71,2 ±â€¯1.3%. The formulations did not demonstrated cytotoxicity under the conditions assessed. Nerolidol 300 mg/kg inhibited neutrophils migration into joint cavity by 18.8% remains compared with control group, and nano-encapsulated nerolidol 3 mg/kg inhibited (26.7% remains) similar to free nerolidol 10 mg/kg (27.4% remains). Histological, quantification of pro-inflammatory and anti-inflammatory cytokines proves the same results. In conclusion the data suggests that nanoencapsulation of nerolidol improved its anti-inflammatory effect on arthritis in mice.