K. Antonio Cárdenas-Noriega

Background: Phytocannabinoids such as cannabidiol (CBD) and cannabigerol (CBG) have received increasing attention in the context of inflammatory and intestinal disorders. However, direct comparisons between their individual and combined effects, as well as the influence of delivery systems, remain limited. Objectives: This study evaluated the biological effects of free and nanoencapsulated CBD and CBG, including a cannabinoid–Eudragit L100 formulation, in an in vitro TNBS-treated intestinal cell model and an in vivo murine model of TNBS-induced colitis. Methods: Cytotoxicity and treatment-associated effects of CBD, CBG, their 1:1 combination, and a nanoencapsulated formulation were assessed in TNBS-exposed Caco-2 cells. In parallel, BALB/c mice with TNBS-induced colitis were evaluated for colonic damage and inflammatory markers. Results: CBD and CBG individually showed dose-dependent effects in Caco-2 cells, while their combined administration produced a greater effect than either compound alone at higher concentrations. The nanoencapsulated formulation preserved cellular metabolic activity following TNBS exposure. In vivo, both free combined and nanoencapsulated cannabinoids were associated with reduced epithelial damage and inflammatory alterations. Conclusions: Nanoencapsulation using Eudragit L100 modulated the biological effects of CBD and CBG in experimental models of TNBS-induced intestinal injury.