These constraints could potentially be surpassed through the utilization of enabling delivery systems. These systems may have the capacity to maintain and improve the functionality of bioactive molecules, enhancing their bioaccessibility and bioavailability, while also enabling a controlled and sustained release [5]. In this context, a range of formulations aimed at oral delivery of cannabinoids has been reported. Self-nano-emulsifying drug delivery systems (SNEDDS) have demonstrated that lipid type--either medium- or long-chain triglycerides--influences the bioavailability and lymphatic uptake of CBD, with long-chain triglycerides improving systemic availability and reducing first-pass metabolism [6]. Similarly, controlled-release and gastro-retentive formulations help extend cannabinoids' narrow absorption window in the upper gastrointestinal tract, which is essential for conditions requiring steady therapeutic levels, such as chronic pain and epilepsy. These gastro-retentive tablets, based on egg albumin and surfactants, have shown improved bioavailability and extended release when compared to conventional CBD solutions [7]. Cyclodextnis such as \(\alpha\)-CD, \(\beta\)-CD, and \(\gamma\)-CD improve CBD's therapeutic potential by allowing encapsulation within their hydrophobic cavities, enhancing solubility and cytotoxic efficacy against cancer cells [8]. Moreover, innovative formulation techniques involving cyclodext and mesoporous silica have proven effective in enhancing the solubility of cannabidiol (CBD), thereby contributing to improved therapeutic outcomes [9] However, cetyltrimethylammonium bromide (CTAB)-modified cellulose nanocrystals (CNCs) have never been tested for encapsulation of CBD. The CTAB-modified surface creates a hydrophobic interface on CNCs, enhancing compatibility with lipophilic compounds like cannabinoids, being a potentially superior alternative for its delivery. These systems have demonstrated high encapsulation efficiencies, often exceeding 90%, and exhibited sustained release properties, beneficial for chronic cannabinoid therapies [10; 11; 12; 13]. Unlike cyclodext or lipid-based SNEDDS, CTAB-modified CNCs offer a more straightforward, scalable approach using renewable cellulose, making them a highly sustainable option. Additionally, its positive surface charge is expected to improve intestinal absorption by interacting favorably with cellular membranes, promoting better uptake.  
This work pioneers the use of CNC-CTAB structures as vehicles for the delivery of CBG, as a means to offer an efficient and sustained release of this molecule and promote its intestinal biological functions. The compatibility of the designed delivery system was evaluated via in vitro cytotoxicity studies toward intestinal cells to confirm a safe application. The biological potential of the delivery system was assessed via in vitro experiments, investigating antioxidant, antimicrobial, and anti-inflammatory activities. Moreover, an in vitro model mimicking gastrointestinal (GI) digestion was employed to evaluate how the digestion conditions influenced the release profile of CBG. As per our knowledge, this is the first study investigating CNC-CTAB structures for the delivery of CBG, providing for the first time comprehensive evaluations of encapsulation and release properties, intestinal cytotoxicity, and biological potential of CNC-CTAB-encapsulated CBG. These findings offer novel insights into the applicability and therapeutic potential of CNC-CTAB as a promising platform for CBG delivery.