In vitro digestion and cytotoxicity study of cannabidiol-loaded nanostructured lipid carriers

Cannabidiol (CBD), a lipophilic compound with promising health benefits, such as analgesic, anti-inflammatory and neuroprotective effects, is characterized by low oral bioavailability, which limit its therapeutic application. To address these limitations, CBD was incorporated into nanostructured lipid carriers (NLCs), either as CBD-rich extract (CBD_ext) or as an isolate (CBD_iso). The resulting systems - NLC-CBD_ext and NLC-CBD_iso - were subjected to in vitro digestion using the standardized INFOGEST protocol. The results demonstrated that NLCs significantly improved in vitro CBD bioaccessibility (86 ± 1 % for NLC-CBD_ext and 94 ± 4 % for NLC-CBD_iso) during simulated digestion compared to control formulations consisting of both CBD forms dispersed in hemp seed oil (HSO), which were 77 ± 4 % and 76 ± 5 % for HSO-CBD_ext and HSO-CBD_iso, respectively. Overall, no significant differences were found between NLC-CBD_ext and NLC-CBD_iso, indicating that both NLC formulations are similarly effective in delivering CBD. Furthermore, cytotoxicity assessments revealed that while both forms of free CBD exhibited dose-dependent cytotoxicity against Caco-2 cells, its incorporation into NLCs maintained >80 % cellular viability. These in vitro findings demonstrate that NLCs are promising food-grade carriers for both CBD forms, but further in vivo validation is required prior to stablishing the real potential for functional foods or therapeutic applications.