Chitosan-Based Polymeric Lipid Nanocapsules Loaded with Cannabis sativa L. Extract: Influence of Lipid Core Composition on Physicochemical Stability and Preliminary Anti-Chikungunya Virus Activity

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.