Characterization and bioactivity of copaiba essential oil carried in a self-nanoemulsifying drug delivery system

Abstract

Copaiba essential oil (CEO) is the volatile part of copaiba balsam, which has been topically used for various inflammatory conditions. However, there are some concerns about the CEO safety for oral use. The lipophilic character of CEO also limits its application in the pharmaceutical field. This study prepared a self-nanoemulsifying drug delivery system (SNEDDS) containing CEO and evaluated its toxic effects against a primary culture from pig liver (PLP2) and Green monkey kidney cell line (Vero). The inhibition of oxide nitric production was also evaluated on RAW 264.7 macrophage cell line to access the anti-inflammatory effect. The CEO was extracted by hydrodistillation and β-caryophyllene accounted for 51.8% of the oil. The formulation (FSNEDDS) consisting of CEO, Cremophor and ethyl linoleate was characterized in relation to morphology, stability, rheology, simulated digestion and bioaccessibility in vitro. FSNEDDS displayed Newtonian flow behavior with viscosity depending only on temperature and, in an aqueous medium, it formed small spherical particles (<100 nm size diameter). The FSNEDDS showed higher oxidative stability than the non-formulated CEO. In the simulated digestion, FSNEDDS formed nanoemulsifying droplets in gastric phase and tiny micelles in intestinal phase, and a bioaccessibility of 63%. The FSNEDDS showed a superior anti-inflammatory activity (+11%) than non-formulated CEO and this beneficial concentration was achieved with a non-toxic concentration for none of the cell lines tested. In conclusion, FSNEDDS improves the physicochemical stability, bioaccessibility and bioactivity of CEO, and it could be a phytotherapic option for per oral administration to treat inflammatory diseases.