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 selfnanoemulsifying
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.
The authors wish to thank the financial support of the Coordenaç˜ao
de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and of the
Conselho Nacional de Desenvolvimento Científico e Tecnológico
(CNPq). The authors are grateful to the Foundation for Science and
Technology (FCT, Portugal) for financial support through national funds
FCT/MCTES (PIDDAC) to CIMO (UIDB/00690/2020 and UIDP/00690/
2020) and SusTEC (LA/P/0007/2020). The authors also thank the National
funding by FCT - Foundation for Science and Technology, through
the institutional scientific employment program-contract with L. Barros
and F. Mandim PhD grant (SFRH/BD/146614/2019).
