Medicinal plants have been explored worldwide as potential alternatives for the prevention and treatment of different diseases, including viral infections. Baccharis crispa Spreng. (Asteraceae) is a native medicinal species widely used in South America. Given the influence of genetic and environmental factors on secondary metabolites biosynthesis and accumulation, this study aimed to evaluate the in vitro antiviral activity of four wild populations of B. crispa from Córdoba, Argentina, and assess the variability in their bioactivity and chemical composition. The cytotoxicity of chloroform, ethanol, and aqueous extracts from aerial parts was evaluated by the neutral red uptake method. Antiviral and virucidal activity against herpes simplex virus type 1 (HSV-1) and chikungunya virus (CHIKV) were assessed via plaque-forming unit (PFU) reduction assay. Phytochemical analyses of the extracts were conducted using HPLC-ESI- MS/MS. The Puesto Pedernera population showed the strongest antiviral activity, with inhibition rates of 82% for CHIKV and 79% against HSV-1, as well as potent virucidal effects, reducing PFU formation by up to 5 logarithms for both viruses. Remarkably, ethanol extract exhibited the least toxicity and strongest inhibitory activity. Villa del Parque population was inactive. We identified 38 secondary metabolites, predominantly phenolic acids (12) and flavonoids (18), in varying proportions. Delphinidin and delphinidin-3-glucoside are described for the first time in the species. Differences in phytochemical profiles were observed among extract types and populations. Key phenolic compounds showed moderate positive correlations with the evaluated bioactivities, emphasizing the complexity of phytochemical properties and interactions. These results highlight the therapeutic potential of B. crispa extracts against viral infections and underscore the importance of considering the geographical source of plant material in bioactivity evaluations.

Cannabidiol (CBD), the main non-intoxicating phytocannabinoid of Cannabis sativa, is highly lipophilic and poorly water-soluble. We developed chitosan-coated lipid nanocapsules (NCs) loaded with a CBD-rich Cannabis sativa ethanolic extract (CEE), using medium-chain triglyceride (MCT) oil or olive oil as the lipid core and optimizing them with a Box–Behnken design; oil and Tween^® 80 volumes mainly determined hydrodynamic diameter and polydispersity. The optimized MCT oil and olive oil NCs had hydrodynamic diameters of 206.9 and 231.2 nm, PDI values of 0.130 and 0.196, zeta potentials of about +31 and +33 mV, and CBD encapsulation efficiencies above 85%. ATR-FTIR suggested different lipid organization and CBD environments in each core, while confocal microscopy located the CBD-reactive signal in the oil phase without resolving the core from the interface. MCT oil NCs retained more CBD at room temperature, but differences under other conditions were small, and the extract dissolved in the same oils behaved similarly, indicating a major contribution of the oil vehicle. Both NCs retained CBD between pH 5.5 and 7.4 and could be redispersed after freeze-drying. In a preliminary chikungunya virus assay, CEE-loaded NCs inhibited the cytopathic effect by 34–45% at non-cytotoxic concentrations, but free CEE in oil was at least as active.