Microemulsions containing Copaifera multijuga Hayne oil-resin: Challenges to achieve an efficient system for beta-caryophyllene delivery

beta-Caryophyllene (beta-CP) is a bioactive sesquiterpene abundant in copaiba oil-resin (COR), which is widely used in Brazilian folk medicine; however, its instability due to the presence of unsaturations is an obstacle to the use of COR in its natural form. Therefore, the development of a system for beta-CP delivery, like the one proposed herein for the first time, may protect it and preserve its therapeutic action. Pseudo-ternary phase diagrams were constructed in this study to obtain COR-containing nanocarriers. Two microemulsions (MEs) were obtained, namely a) ME-I containing (% w/w) 47.1 water, 8.5 Plurol Oleique, 33.8 Labrasol and 10.6 COR and b) ME-II containing (% w/w) 39.0 water, 18.3 Plurol Oleique, 36.6 Labrasol and 6.1 COR. Both MEs showed physicochemical properties suitable for a delivery system such as pH 5.25-5.74, conductivity of 79.5-120.9 mu S cm(-1) and slightly negative Zeta potential (-3.57/-2.63 mV). Transmission electron microscopy revealed the nanometric size of MEs droplets, differential scanning calorimetry their oil/water nature, while refractive indices clarity and isotropicity. Both systems behaved as Newtonian fluids and exhibited low viscosity (64.42 +/- 0.667 mPa.s for ME-I and 118.78 +/- 0.503 mPa.s for ME-II). After COR incorporation in MEs, steam distillation allowed obtaining beta-CP contents depending on their initial COR amount. The pharmacological effectiveness of these innovating systems for beta-CP delivery was confirmed by antimicrobial and anti-inflammatory activity tests. ME-II afforded a stronger antimicrobial effect against all target microorganisms than ME-I and a much stronger one than COR. Carrageenan-induced inflammation in rat paw was visibly inhibited by MEs.