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Bioavailability for the Improved Therapeutic Profile of trans-Dehydrocrotonin Incorporated into a Copaiba Oil Self-Nanoemulsifying Drug Delivery System: Formulation, Physicochemical Characterizations, and Antioxidant In Vitro Effect

Year: 2025

Type: article

Abstract: Croton cajucara Benth and Copaifera reticulata Ducke are prominent species in the traditional medicine of the Amazon region of Brazil. Copaifera species produce oil resin rich in bioactive diterpenes, and C. cajucara is a prolific producer of the diterpene 19-nor-clerodane trans-dehydrocrotonin (t-DCTN). This research aimed to develop a self-nanoemulsion drug delivery system (SNEDDS) by using copaiba oil resin (C. reticulata) as a carrier for t-DCTN. A stable SNEDDS single-phase nanoemulsion comprising Tween 80 (7%, w/w) and copaiba oil (0.5%, w/w) afforded a fine oil-in-water carrier system (SNEDDS-CO). The dropwise solubilization of t-DCTN (1 mg) into SNEDDS-CO resulted in the nanoformulation called SNEDDS-CO-DCTN. Transmission electron microscopy (TEM) analysis revealed spherical nanodevices, while particle size, polydispersity index (PDI), and zeta potential measurements indicated small nanodroplets (about 10 nm), uniformly distributed (between 0.1 and 0.2) and negatively charged for both systems. The in vitro kinetic of t-DCTN-loaded (SNEDDS-CO-DCTN) analyzed by using simulated conditions of the gastrointestinal microenvironment, as perspective for oral drug delivery, showed a controlled release profile, and corresponded to the Fickian diffusion model. The in vitro antioxidant activity of the samples (t-DCTN, SNEDDS-CO, and SNEDDS-CO-DCTN) was confirmed through total antioxidant capacity (TAC), reducing power, copper ion chelation, and hydroxyl radical scavenging assays. The antioxidant activity of SNEDDS-CO-DCTN which contained 1 mg of t-DCTN per mL−1 of the carrier SNEDDS-CO was similar or even better when compared to the unload t-DCTN solubilized in DMSO (10 mg mL−1). The SNEDDS formulations herein described were successfully obtained under moderated and controlled conditions, exhibiting effective physicochemical data and release characteristics with huge bioaccessibility for co-loading copaiba oil and t-DCTN. The novel colloidal system SNEDDS-CO-DCTN is a potential antioxidant nanoproduct and, from now on, is available for further pharmacological investigations.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26104469