Cellulose nanocrystal stabilised Pickering emulgels for sustained colonic delivery of budesonide

Inflammatory Bowel Disease (IBD) is a chronic gastrointestinal condition that could benefit from targeted drug delivery strategies to minimise systemic side effects. Conventional therapies often lack site specificity, limiting their effectiveness. Here, emulgels stabilised by cellulose nanocrystals (CNC) and reinforced with α-cyclodextrin/polyethylene glycol (α-CD/PEG) supramolecular gels were explored as a novel platform for the local delivery of budesonide to the gastrointestinal tract. CNC-stabilised Pickering emulsions (40-70% v/v oil, 0.5-2 mg·mL⁻¹ CNC) were characterised for droplet size, zeta potential, stability, and rheology. Emulgels were obtained by incorporating α-CD (6-10% w/v) and PEG (5-10% w/v, 10 and 20 kg/mol) in the aqueous phase. These systems were assessed for long-term stability, rheological properties, drug release, mucoadhesion, cytocompatibility, and drug permeability in Caco-2 cell monolayers. Emulsions showed enhanced stability with increasing CNC concentration and oil fraction. Incorporating a gel phase of α-CD/PEG markedly increased the storage modulus, G' up to 1.53 × 10⁵ Pa without phase separation over 30 days. The emulgels shear-thinned and quickly recovered after release of the strain, equally after injection through a synringe, and displayed mucoadhesiveness to porcine intestinal tissue. Budesonide was efficiently loaded (86-98%) and released in a sustained manner over 72 h. Permeation studies confirmed epithelial drug transport, which was reduced compared to solution, consistent with controlled release. The emulgels did not compromise epithelial barrier integrity and were non-toxic to Caco-2 cells. Overall, CNC-stabilised α-CD/PEG emulgels demonstrate high stability, biocompatibility, and tunable release, making them promising candidates for localised IBD therapy.