Nanoformulations based on Copaifera reticulata Ducke and trans-dehydrocrotonin: physicochemical characterizations and evaluation of antioxidant and cytotoxic effects
Copaifera reticulata Ducke; trans-dehydrocrotonin; SNEDDS systems; physicochemical characterizations; antioxidant and citotoxic analysis.
Despite the numerous advances in the pharmaceutical industry and the development of techniques and materials applied in the health area, phytotherapy as a form of traditional medicine remains in vogue and gains followers in all segments of society. Among the natural resources from Brazilian biodiversity, the copaiba oil obtained from species of the genus Copaifera and the bioactive trans-dehydrocrotonin (t-DCTN), obtained from the stem bark of Croton cajucara Benth, which are representatives of popular medicine originating in the Amazon region of Brazil, with great importance in the treatment and cure of various diseases. The main objective of this research was to develop a colloidal nanoformulation SNEDDS-type (Self-nanoemulsifying Drug Delivery System) based on copaiba resin oil [Copaifera reticulata Ducke (OCPR)], as a carrier system of the bioactive t-DCTN. Among the physicochemical analyses, the size of the nanodroplets (nm), polydispersivity index (PDI) and Zeta potential (mV) of the SNEDDS-OCPR-DCTN formulation were obtained, which presented respectively 11.66 nm, 0.17 and -3.85 mV. The bioactive t-DCTN reached a maximum cumulative sustained release of 90.33 ± 0.01% (360 minutes). The antioxidant effect of the nanoformulation SNEDDS-OCPR-DCTN was evaluated through in vitro experiments, showing effective results in the tests of reducing activity equivalent to ascorbic acid, reducing power in neutral medium and chelating activity of copper ions. The cytotoxic activity was evaluated by the MTT [(3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide] method. Macrophages and murine fibroblasts of the L-929 lineage, were used for the cell viability testes. The findings showed that SNEDDS OCPR-DCTN at concentrations of 100 μg/mL and 200 μg/mL inhibited 99% of fibroblasts. At concentrations below 25 μg/mL the viability of fibroblasts exceed 70%. In contrast, the system demonstrated a distinct behavior in relation to macrophages, maintaining the cell viability above 50% at highest concentrations. For the L-929 lineage, an IC50 of 35.54 μg/mL was observed, with a confidence interval of 31.12- 40.74 and R² = 0.969.