Nanoemulsion Improves the Anti-inflammatory Activity of Carvacrol upon Oral Administration

Carvacrol is the main phenolic monoterpene isolated from the essential oils of plants from the genus Origanum L., Lamiaceae. Carvacrol has several biological activities, including antioxidant, antimicrobial and anti-inflammatory activities. The present study aimed to develop a carvacrol-loaded nanoemulsion and evaluate whether it improves the anti-inflammatory activity of the oil. A nanoemulsion was produced and its average droplet size, polydispersity index, and zeta potential were characterized. To evaluate its anti-inflammatory activity, a complete Freund's adjuvant-induced paw edema mouse model was used, and interleukin (IL)-1 beta levels were quantified using ELISA. To assess toxicity, behavioral changes and biochemical parameters in mice were evaluated. The nanoemulsion was shown to be 125.00 +/- 0.782 nm in size, with a polydispersity index of 0.200 +/- 0.001 and zeta potential of - 26.37 +/- 0.59 mV. After intraperitoneal administration, carvacrol and the carvacrol-loaded nanoemulsion showed similar anti-inflammatory efficacy as dexamethasone. Notably, both tested samples had longer anti-inflammatory effects than the control drug. The pharmacological profiles of orally administered carvacrol and its nanoemulsion were different. Although carvacrol (200 mg/kg) did not exhibit anti-inflammatory activity upon oral administration, carvacrol-loaded nanoemulsion administered at the same dose and route induced an anti-edematogenic effect that persisted for up to 24 h. Oral administration of carvacrol-loaded nanoemulsion, but not carvacrol, reduced pro-inflammatory cytokine IL-1 beta levels in the inflamed mouse paw, with similar efficacy to dexamethasone. Moreover, daily treatment with carvacrol-loaded nanoemulsion did not induce any behavioral or biochemical alterations. Nanoemulsification improved the pharmacological properties of carvacrol.